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EXPERIMENTAL 

PHARMACOLOGY 


BY 

DENNIS  E.  JACKSON,  Ph.D.,  M.D. 

ASSOCIATE    PROFESSOR    OF    PHARMACOLOGY,    WASIllKGTON    UNIVERSITY 
MEDICAL    SCHOOL,    ST.    LOUIS. 


WITH  THREE  HUNDRED  NINETY  ORIGINAL  ILLUSTRA- 
TIONS INCLUDING  TWENTY-FOUR  FULL-PAGE 
COLOR   PLATES 


ST.  LOUIS 

C.  V.  MOSBY  COMPANY 

1917 


Yyj^A. 


Copyright,  1917,  By  C.  V.  Mosby  Company 


Press  of 

C.   V.  Mosby  Company 

St.   Louis 


PREFACE. 

For  several  years  the  writer  has  liad  a  growing  convic- 
tion that  the  teaching  of  pharmacology  might  l^e  greatly 
facilitated,  and  rendered  much  more  effective  and  compre- 
hensive, if  each  student  could  have  in  his  own  hands  a 
laboratory  manual  giving  exact,  specific,  detailed  directions 
for  carrying  out  most  of  the  experiments  which  he  will 
be  called  upon  to  perform  in  the  study  of  this  most  inter- 
esting, vital  and  complex  subject.  The  small  number  of 
manuals  of  this  character  w^hich  heretofore  have  appeared 
in  this  field  may  be  most  strikingly  compared  with  the  very 
large  number  of  laboratory  manuals  which  have  been  pub- 
lished on  such  subjects  as  chemistry,  botany,  physics, 
zoolog}^,  etc.  And  the  thoughtful  teacher  might  be  at  once 
inclined  to  ask  himself  whether  or  not  the  general  scope 
and  character  of  the  work  .done  in  these  various  experi- 
mental fields  may  not  have  been  to  some  extent  indicated 
by  the  number  and  character  of  experimental  manuals  de- 
voted to  these  subjects.  In  consideration  of  these  points 
the  author  has  therefore  ventured  to  hope  that  in  present- 
ing this  manual  of  experimental  pharmacology^  to  teachers 
and  students,  some  small  amount  of  good  may  be  accom- 
plished. 

My  especial  thanks  are  due  to  the  publishers,  Avho  have 
rendered  every  assistance  they  could  in  the  progress  of 
this  work;  to  Mr.  Paul  Knabe,  who  has  faithfully  devoted 
much  time  and  labor  to  the  proof  reading,  the  arrangement 
of  the  illustrations,  and  the  printing  of  the  book;  and  to 
Mr.  Paul  P.  Halleck,  who  in  making  the  drawings  contained 
herein  has  given  me  the  advantage  both  of  his  extensive 
experience  as  an  artist,  and  of  his  special  training  as  a 
physician.    I  am  deeply  indebted  to  Mr.  John  A.  Higgins, 


4  PKEFACE 

who  for  seven  years  has  faithfully  assisted  me  in  per- 
forming most  of  the  experiments  from  which  the  tracings 
illustrated  in  this  book  have  been  mainly  derived. 

D.  E.  J. 
Pharmacological  Laboratory, 
Washington  University  Medical  School. 


CONTENTS. 
PART  I. 

PRELIMINARY  EXERCISE. 

PAGE 
Assignment  of  Tables  and  Permanent  Apparatus     ......       33 

EXPERIMENTS. 

I.  Ether.  (Action  on  the  Central  Nervous  System. — Cerebrum.)  .  .  53 
Chloroform.       (Action    on    the    Central    Nervous    System. — Optic 

Lobes.) 55 

Ether,  Ethyl  Chloride,  Chloroform,  Ethyl  Bromide.      (Irritability 

and  Conductivity  of  Nerve.) 57 

Ethyl   Chloride.      (Local  Anesthesia.) 64 

II.  Ether.      (Action  on  the  Heart. — Dissection  for  the  Vagus  Nerve 

in    the    Frog.) 65 

Chloroform.      (Action  on  the  Frog's  Heart.) 70 

Chloroform.      (Action  on  Lymph  Hearts.)        70 

III.  Turtle:    Vagus  Dissection.      (Action  of  Ether  on  the  Heart.)      .     .  71 
Chloroform.      (Action  on  the  Turtle's  Heart.) 76 

IV.  Ether,   Chloroform,   Ethyl   Bromide.      (Dog:     Respiration,   Blood- 

pressure,  Cervical  Vagi,   and   Sympathetics.) 77 

Anesthetization  of  the  Animal 77 

Insertion  of   Tracheal   and   Carotid  Cannulas;    Isolation   of   Vagi 

and   External   Jugular   Vein 85 

Insertion  of   Femoral  Injecting   Cannula ;   Dissection   of   Femoral 

Artery  and  Vein  and  Saphenous  Nerve 93 

Recording   Blood-pressure 96 

Recording  Respiration 97 

Adjustment  of  Writing  Points 98 

Other  Methods  of  Recording  Respiration 98 

Beginning   of   the   Records 99 

V.  Ether,  Chloroform,  Ethyl  Bromide.      (Dog:     Motor  Areas,  Blood- 
pressure,  Blood,  Heart.) 103 

Dissection  of  Pulmonary  Artery  and  Vein 112 

VI.  Nitrous  Oxide,  Carbon  Dioxide,  Oxygen.     (Frog:    Central  Nervous 

System.) .113 

VII.  Nitrous  Oxide,  Ethyl  Chloride,  Carbon  Dioxide,  Increased  Atmos- 
pheric Pressure,    (Decreased  Atmospheric  Pressure.)      (Frog, 

Guinea  Pig,  Rat,  Kitten,  or  Pup.) 117 

Paul   Bert's   Experiment 120 


6  CONTEjSTTS 

PAGE 
VIII.  The   Closed    Method   of   Anesthesia.      For    Ether,   Chloroform, 
Ethyl  Chloride,  Ethyl  Bromide,  (Nitrous  Oxide),  ''Somno- 
form, "    etc.,    with   Oxygen,    Student    Method.      (Dogs    or 

Cats.) 121 

IX.  Intratracheal  Insufflation 129 

X.  Alcohol.      (Frog:     Central  Nervous   System,  Heart  and  Vago- 
sympathetic Nerve.) 13.3 

XI.  Alcohol.      (Turtle:    Heart  and  Vagus  Nerve.) 135 

XII.  Ethy]  Alcohol,  Brandy,  Whiskey,  Wine,  Methyl  Alcohol,  Amyl 

Alcohol.     (Dog:    Blood-pressure,  Eespiration,  Esophagus.)      136 

XIII.  Whiskey  or  Brandy.      (Reaction   Time.) .     144 

XIV.  Alcohol,  Whiskey,  Brandy,  Wine.      (Dog  or  Cat:     Myocardio- 

graijLic  Tracings,  Cardiac  Sympathetic  Nerves.)      ....     147 

XV.  Antiseptic  Action  of  Alcohol 157 

XVI.  Alcohol,   Brandy,   Urethane,    Chloral.      (Dog:     Blood-pressure, 

Resj^iration,  Cerebrospinal  Fluid,  Kidney  or  Sjjleen.)      .     .     158 
XVII.  Chloral  Hydrate,  Urethane,  Paraldehyde,  Chloretone.     (Frogs: 

Central  Nervous  System.) 168 

XVIII.  Chloral   Hydrate.      (Action   on   the   Frog's  Heart.)      ....     169 
XIX.  Chloral     Hydrate.        (Frog:      Retinal     Circulation     With     the 

Ophthalmoscope.) 169 

XX.  Chloral  Hydrate,  Adrenaline.      (Turtle's  Heart.)      ......     172 

XXI.  Chloral   Hydrate   and   Alkalis 172 

XXII.  Morphine.     (Frog:    Central  Nervous  System.) 172 

XXIII.  Thebaine,  Codeine.     (Frog:    Central  Nervoiis  System.)      .     .     .     173 

XXIV.  Morphine.      (Chemical  Test  for  Morphine.) 173 

XXV.  Morphine.     (Dog:    Respiration,  Excretion,  Pupils,  Central  Ner- 
vous System,  General  Symptoms.) 175 

XXVI.  Fehling's   Test   for   Reducing   Bodies 176 

XXVII.  Morphine.        (Cat:       General      Symptoms,     Central      Nervous 

System.) 177 

XXVIII.  Morphine,  Codeine.      (Dog:    Respiration,  Blood-pressure,  Oxy- 
gen Consumption,  Urine.) 177 

XXIX.  Morphine,  Codeine,  Pantopon,  Heroine,  Peronine,  Dionine,  Nar- 

cotine  or  Thebaine.      (Spinal  Dog:     Bronchioles.)      .     .     .     194 
XXX.  Heroine  or  Codeine.     (Spinal  Dog:    Blood-pressure,  Lung  Vol- 
ume  and   Bladder    Contractions.) 206 

XXXI.  Strychnine.      (Frog:    Action  on  the  Cord.) 217 

XXXII.  Strychnine.      (Frog:    Heart  and  Vago-sympathetic  Nerve.)      .     220 

XXXIII.  Strychnine.      (Turtle:    Heart  and  Vagus  Nerve.) 220 

XXXIV.  strychnine.      (Dog:     Blood-pressure,  Respiration,  and  Kidney, 

Spleeii  or  Intestinal  Loop.) 222 

XXXV.  Strychnine.  (Ether,  Morphine,  Chloral  Hydrate.)  (Dog: 
Blood-pressure,  Respiration,  Oxygen  Consumption,  Air  Em- 
bolism.)        226 


CONTENTS 


PAGE 

XXXVI.  Strychnine.      (Student:     Reaction    Time.) 2.30 

XXXVII.  Picrotoxine.     (Frog:    Action  on  Medulla  and  Cord.)      .     .     .  2.31 
XXXVIII.  Picrotoxine,  Chloretone.      (Dog:     Blood-pressure,  Respiration 

and  Kidney,   Spleen  or  Intestinal   Loop  Volume.)      .     .  23.3 

XXXIX.  Hydrastine.      (Frog:    Spinal  Cord.) 238 

XL.  Hydrastine.      (Frog:    Heart  and  Vagus  Nerve.) 240 

XLI.  Hydrastine.      (Turtle:    Heart  and  Vagus  Nerve.)      ....  241 

XLII.  Caffeine.      (Frog:     Central  Nervous  System,  Muscles.)       .     .  241 

XLIII.  Caffeine.      (Frog:    Muscle  and  Nerve.) 243 

XLI V.  Caffeine.      (Frog:    Heart  and  Vagus  Nerve.) 244 

XLV.  Caffeine.      (Turtle:     Heart  and  Vagus  Nerve.) 244 

XL VI.  Caffeine.      (Man:     Reaction    Time.) 244 

XLVII.  Caffeine.      (Frog:    Muscular  Work.) 245 

XLVIII.  Caffeine.      (Rabbit:    Diuresis,  Cervical  Nerves,  Depressor.)      .  247 
XLIX.  Caffeine,  Sodium  Sulphate.     (Dog:    Blood-pressure,  Diuresis, 

Respiration,   Sciatic   Nerve.) 249 

L.  Diuretine,  (Sodium-theobromine-salicylate),  Agurine,  (So- 
dium-theobromine-acetate).  (Rabbit:  Diuresis  and  Res- 
piration.)       253 

LI.  Urea,  S.  A.  Matthews'  Solution,  or  Saline  Diuretics.      (Rab- 
bit or  Cat:    Diuresis.) 254 

LII.  Curara.      (Frog:    General    Action,    Claud    Bernard's    Experi- 
ment.)        255 

LIII.  Curara.      (Frog:    Heart  and  Vago-sympathetic  Nerve.)      .     .  257 

LFV.  Curara.      (Turtle:    Heart  and  Vagus  Nerve.) 257 

LV.  Curara,  Strychnine.      (Dog  or  Cat:    Blood-pressure,  Respira- 
tion, Urine,  Sciatic  Nerve.     Dog:     Salivary  Ducts  and 

Nerves.)       257 

Dog 250 

LVI.  Coniine.      (Frog:    Heart  and  Vagus  Nerve.) 260 

LVII.  Coniine.      (Turtle:    Heart  and  Vagus  Nerve,  Lungs  and  Sym- 
pathetic Nerves.) 260 

LVIII.  Coniine.      (Dog:    Blood-pressure,  Respiration,  Salivary  Glands 

and  Kidney,   Spleen  or'  Intestinal  Loop.) 265 

LIX.  Atropine.      (Frog:    Heart    and   Vagus    Nerve.) 268 

LX.  Atropine.     (Frog:    Muscle    and    Nerve) 269 

LXI.  Atropine.      (Turtle:    Heart  and  Vagus  Nerve.) 269 

LXII.  Atropine.      (Cat,  Guinea  Pig,  Rat,  Dog,  Pigeon,  or  Chicken: 

Pupil.) 269 

LXIII.  Atropine.      (Dog,  Cat  or  Rabbit :    Blood-pressure,  Respiration, 
Heart   and  Vagus  Nerve, — Dog,  Salivary  Secretion  and 

Chorda  Tympani,  Sweat  Nerves,  Pancreatic  Secretion.)  270 

LXIV.  Scopolamine.      (Frog:     General   S%inptoms.) 273 

"    LXV.  Pilocarpine,  Atropine.      (Frog:    Heart  and  Vagus  Nerve.)      .  273 
LXVI.  Pilocarpine  or  Arecoline  and  Atropine.      (Frog:   Retinal  Cir- 
culation.)       274 


CONTENTS 


LXVII. 

LXVIII. 

LXIX. 

LXX. 

LXXI. 

LXXII. 
LXXIII. 
LXXIV. 

LXXV. 

LXXVI. 

LXXVII. 
LXXVIII. 


LXXIX. 

LXXX. 

LXXXI. 


LXXXII. 
LXXXIII. 


LXXXIV. 

LXXXV. 

LXXXVl. 

LXXXVII. 
LXXXVIII. 

LXXXIX. 


xc. 


Pilocarpine  or  Arecoline  and  Atropine.     (Dog,  Cat,  Eabbit, 

and  Pigeon  or  Chicken:    Pupil.) 275 

Pilocarpine,  Atropine.      (Dog:    Blood-pressure,  Kespiration, 

Salivary   and   Pancreatic    Secretions.) 275 

Pilocarpine,  Arecoline,  Adrenaline,  Atropine,  and  Barium. 

(Dog:    Bladder,  Intestine,  Eespiration,  Blood-pressure.)     278 
Pilocarpine,     Adrenaline,     Arecoline,     Atropine,      Barium. 

(Spinal   Dog:     Blood-pressure   and   Bronchioles.)      .     .     287 

Nicotine.      (Frog:    General  Symptoms.) 300 

Nicotine.      (Frog:    Heart  and  Vagus  Nerve.) 300 

Nicotine.      (Turtle:    Heart   and   Vagus   Nerve.)      ....     301 

Nicotine.      (Turtle:    Lungs.) 302 

Nicotine,  Arecoline,  Atropine.     (Dog :     Blood-pressure,  Ees- 
piration, Limb  Volume,  Litestinal  Contraction.)    .     .     .     304 
Nicotine,  Adrenaline,  Pilocarpine,  Atropine.     (Dog:    Blood- 
pressure,  Intraocular  Pressure,  Eespiration  and  Kidney, 

Spleen  or  Intestinal  Loop  Volume.) 307 

Nicotine,  Adrenaline,  Barium.  (Dog:  Pulmonary  Blood- 
pressure,  Carotid  Pressure.) 310 

Nicotine,  Pilocarpine,  Atropine.  (Dog:  Intraocular  Nerves, 
Salivary   Glands,   Oxygen   Consumption,   Blood-pressure 

and    Eespiration.)        318 

Lobeline.     (Frog  or  Turtle:     Heart  and  Inhibitory  Nerves.)      322 
Lobeline,  Pilocarpine.      (Turtle:     Lung  Tracings.)      .     .     .     322 
Lobeline,  Adrenaline,  Pilocarpine,  Tetramethylammonium 
chloride.      (Dog:    Bladder  Contraction,  Blood-pressure, 

Eespiration,  Pupil.) 325 

Lobeline,  Nicotine,  Pilocarpine.     (Guinea  Pig,  Cat,  Dog,  or 

Eabbit;    Uterus    Strip.) 332 

Adrenaline,  Lobeline,  Nicotine,  Pilocarpine,  Atropine. 
(Guinea  Pig,  Eabbit,  Dog,  Cat,  Frog:  Intestinal  Seg- 
ment.)      .     334 

Muscarine,  Atrop)ine.     (Turtle:    Lung  Tracings.)      ....     336 

Physostigmine.      (Frog:     Heart    Tracing.) 337 

Physostigmine,  Atropine,  (Sodium  Nitrite).  (Frog:  Stom- 
ach Eing.) 337 

Physostigmine.     (Turtle:    Heart  Tracing.) 338 

Physostigmine,    (Adrenaline,    Atropine).      (Turtle:     Lung 

Tracing.)        338 

Physostigmine,  Hyoscine,  Adrenaline,  (Trimethylamine) 
(Dog:  Eespiration,  Blood-pressure,  Intestinal  Contrac- 
tions.)     339 

Adrenaline,   Sodium  Nitrite,  Barium  Chloride.      (Dog,  Cat 

or  Eabbit:     Perfusion  of  Kidney.) 342 


CON^TENTS  y 

PAGE 
XCI.  Physostigmiiie,  Atropine,   (Heroine),  Adrenaline.     (Spinal  Dog 
or  Cat:     Bronchioles,  Blood-pressure,  and  Bladder  Contrac- 
tions.)      , 346 

XCII.  Cocaine.     (Frog:    Central  Nervous  System.) 350 

XCIII.  Cocaine,  Physostigmine.      (Rabbit,  Cat,  Dog,  Pigeon,  Sparrow, 

Chicken,  Rat:     Action  on  Pupil.)      .     .  • 350 

XCIV.  Cocaine,  Novocaine.      (Local  Anesthetic  Action.) 351 

XCV.  Cocaine.      (Frog  or  Turtle:     Heart  Tracings.) 351 

XCVT.  Cocaine.     (Frog:     Action  on  Muscular  Work.)      ......     352 

XCVII.  Cocaine,  Novocaine,  Barium,  Adrenaline.  (Dog  or  Cat:  Res- 
piration, Blood-pressure,  Intraocular  Pressure,  Local  Vascu- 
lar Action  and  Intestinal  Contractions.) 353 

XCVIII.  Novocaine.      (Dog:      Spinal  Anesthesia.) 356 

XCIX.  Ergot.      (Rooster:    Action  on  Comb.) 360 

C.  Ergot.      (Frog:      Capillary   Circulation.) 361 

CI.  Tyramine.      (Frog:    Capillary  Circulation.) 363 

CII.  Ergamine.      (Turtle:    Lung  Tracing.) 363 

cm.  Ergotoxine,  Ergamine,  Adrenaline,  Barium.  (Dog  or  Cat: 
Blood-pressure,  Respiration,  Uterine  Contractions — Bar- 
bour's  Method.) 363 

CIV.  Ergamine,  Adrenaline,  Tyramine,  (Codeine  or  Heroine).     (Dog: 

Blood-pressure,  Pulmonary  Blood-pressure,  Respiration.)      .     369 
CV.  Ergamine,  Adrenaline  (or  Hordenine),  Atropine.     (Spinal  Dog, 

or  Cat:     Bronchioles.) 373 

CVI.  Ergotoxine,  Ergamine.     (Cat,  Guinea  Pig,  Dog,  Rabbit:  Uterine 

Strip.) 380 

CVII.  Ergot.      (Cat:    Action  on  Uterus.) 381 

CVIII.  Pituitrin,  Ergamine,  Adrenaline.  (Dog,  Cat,  or  Rabbit:  Uter- 
ine Contractions,  Blood-pressure.) 382 

CIX.  Pituitrin,   Ergamine,   Levulose,   Adrenaline.      (Dog:      Thoracic 

Duct,  Blood-pressure,  Bladder  Contractions,   Resp)iration.)      384 

ex.  Pituitrin.      (Frog:     Capillary   Circulation.) 387 

CXI.  Pituitrin.      (Frog  or  Turtle:    Heart  Tracing.) 388 

CXII.  Pituitrin.      (Turtle:     Lung   Tracing.) 388 

CXIII.  Pituitrin.      (Guinea  Pig,  Cat,  Dog,  Rabbit:    Uterine  Strip.)      .     390 
CXIV.  Pituitary  Extract,  Adrenaline,  Atropine,  Baiium   (Dog:   Bron- 
chial   Contraction.) 391 

CXV.  Pituitrin,  Adrenaline,  Aconitine.      (Dog:    Urine  Secretion,  In- 
testinal Contractions,  Blood-pressure,  and  Respiration.)      .     392 
CXVI.  Pituitrin,   Adrenaline,    Vanadium.      (Dog:     Pulmonary    Blood- 
pressure.)    394 

CXVII.  Dissection  of  the  Eye. — Its  Anatomy  and  Pharmacology     .     .     .     394 
CXVIII.  Amyl   Nitrite.      (Student:     Plethysmographie   Record,    General 

Action.) 397 


10 


CONTENTS 


CXIX. 

cxx. 

CXXI. 

CXXII. 

CXXIII. 


CXXIV. 

cxxv. 

CXXVI. 

CXXVII. 

CXXVIII. 

CXXIX. 

cxxx. 

CXXXI. 
CXXXII. 


CXXXIII. 
CXXXIV. 

cxxxv. 

CXXXVI. 

CXXXVII. 

CXXXVIII. 

CXXXIX. 

CXL, 

CXLI. 

CXLII. 

CXLIII. 

CXLIV. 

CXLV. 

CXL  VI. 

CXL  VII. 


CXLVIII. 

CXLIX. 

CL, 


PAGE 

Amyl  Nitrite.      (Student:    Pulse  Tracing.) 399 

Amyl  Nitrite.      (Student:    Corpuscles   in   Retinal    Vessels.)  400 

Amyl  Nitrite.      (Student:    Retinal   Blood  Vessels.)      .     .     .  401 

Amyl  Nitrite.      (Student:    Effect  on  Vision.) 403 

Amyl  Nitrite,  Nitroglycerine,  Sodium  Nitrite.  (Dog: 
Bloodri)ressure,  Respiration,  Spleen  or  Intestinal  Loop 

Volume,  Blood.) 404 

Nitrites,  Pilocarpine,  Adrenaline.  (Dog:  Bronchial  Ac- 
tion.)   406 

Digitoxin.      (Frog:    General   Action.) 407 

Digitoxin.      (Frog:    Heart   Tracing.) •  .     .  408 

Digitoxin.      (Turtle:    Heart  Tracing.) 408 

Digitoxin.      (Dog  or  Cat:    Blood-pressure  and  Respiration.)  408 
Digitoxin,  Strophanthin,  Nitroglycerin.      (Dog:    Pulmonary 

Blood-pressure,    Carotid    Pressure.)      .     ., 415 

Digitoxin.     (Dog:    Heart  Tracings,  Carotid  Pressure.)      .     .  418 
Digitoxin,  Strophanthin.      (Dog:     Diuresis,  Spleen  Volume, 

Leg  Volume,  Blood-pressure  and  Respiration.)      .     .     .  420 
Adrenaline,    Potassium    Chloride,    Digitoxin,    Strophanthin. 
(Cat,    Rabbit,    Dog:      Heart    Perfusion — Langendorff 

Method.) 424 

Aconitine.      (Frog:    General  Action.) 428 

Aconitine.      (Frog:    Heart   Tracing.) 429 

Aconitine.      (Turtle:     Heart    Tracing.) 429 

Aconitine.  (Dog:  Blood-pressure,  Respiration,  Tempera- 
ture.)       429 

Aconitine.      (Dog:     Heart    Tracings,   Blood-pressure.)      .     .  431 

Aconitine.      (Student:      Local    Action.) 433 

Veratrine.      (Frog:    General  Action.) 433 

Veratrine.  (Frog  or  Turtle:  Heart  and  Inhibitory  Ap- 
paratus.)      434 

Veratrine.      (Frog:    Skeletal  Muscle.) 434 

Veratrine.      (Turtle:    Lung  Tracing.) 437 

Veratrine,  Adrenaline.     (Dog:    Blood-pressure,  Respiration, 

Intestinal    Contraction.) 437 

Veratrine.      (Dog:     Heart    Tracings,   Blood-pressure.)      .     .  440 

Apomorphine.      (Dog:     Vomiting   Center.) 440 

Ipecac.      (Dog:     Eniesis.) 440 

Sodium  Cyanide,  (Hydrocyanic  Acid),  Sodium  Sulphide, 
Hydrogen  Peroxide.  (Dog:  Respiration,  Blood-pres- 
sure, Oxygen  Consumption,  Blood  Glycosuria.)     .     .     .  441 

Quinine.      (Frog:    General  Symptoms.)        447 

Quinine.      (Frog  or  Turtle:    Heart  Tracing.) 447 

Quinine.  (Frog:  Action  on  White  Corpuscles — Binz's  Ex- 
periment.)         447 


CONTEXTS  11 

PAGE 

CLI.  Antipvrinc.      (Frog:     General    Action.) 449 

CLII.  Antipyrine,  /3-tetrahydronaphtliylamine  Hydrochlorido.     (Dog: 

Respiration,   Blood-pressure,   Leg   Volume.) 449 

•CLIII.  Antipyrine,   Peptone.      (Two    Rabbits:     Temperature   Regula- 
tion.)     451 

CLIV.  Quinine,  Peptone.     (Two  Rabbits:    Tem2:)erature  Regulation.)      451 
CLV.  Phenacetine,   Acetanilide   or    Aspirin    (Acetylsalicylic    Acid). 

(Fevered   Animal:      Temperature.) 451 

CLVI.  Acetylsalicylic  Acid   (Aspirin).      (Student:     Headache.)      .     .     452 
CLVII.  Phenylsalicylate   (Salol).     (Student:    Excretion,  Absorption.)      452 
'CLVIII.  /3-tetraliydronaphtliylamine  Hydrochloride,  Pilocarpine.    (Dog: 

Oxygen  Consumption,   Blood-pressure,   Respiration.)      .     .     45.3 
CLIX.  Carbolic  Acid    (Phenol).      (Frog:     General   Action.)      .     .     .     454 
CLX.  Carbolic  Acid,  Sodium  Sulphate.      (Dog:    Local  Action,  Res- 
piration, Blood-pressure,  Spleen  Volume,  Antidote.)      .     .     454 

CLXI.  Phloridzin,  Adrenaline.      (Rabbit:     Glycosuiia.) 457 

CLXII.  Potassium   Iodide.      (Student:     Absorption,   Excretion.)      .     .     457 
■CLXIII.  Alkalies,  Acids,  Sodium  Nitrite,  Adrenaline.      (Frog:    Perfu- 
sion   of    Vessels.) 458 

CLXIV.  Magnesium,   Calcium.      (Rabbit:     Anesthesia,    Antagonism. — 

Meltzer   and   Auer's   experiment.) 460 

CLXV.  Arsenic.     (Dog  or  Rabbit:    Respiration,  Blood-pressure,  Peri- 
stalsis, Renal  Action,  Blood.) 460 

CLXVI.  Antimony    (Tartar   Emetic).      (Dog:     Emesis.) 462 

CLXVII.  Vanadium,  Sodium  Hydroxide,  Ammonia.  (Dog:  Blood-pres- 
sure, Respiration,  Spleen  Volume,  Reflex  and  Local  Ac- 
tions, Intestinal  or   Bladder  Contractions.) 462 

CLXVIII.  Acid,  Alkali — Rhubarb,  Croton  Oil,  Magnesium  Sulphate. 
(Dog:  Antagonism  of  Acids  and  Alkalies,  Absorption 
and  Excretion  of  Rhubarb,  Local  Action  of  Croton  Oil 
and    Magnesium    Sulphate — Moreau's   Experiment.)      .     .     466 


PAET  II. 

SHOP  WORK. 

The  Shop 470 

Equipment 476 

List    of   Equipment 479 

Mechanical  Procedures 489 

Glass   Blowing 49.3 

Frog  Clips 495 

Brass    Arterial    Cannulas 496 

Stands  and  Castings 496 

Lacquering 49S 


12  CONTENTS 

PHOTOGRAPHY. 

PAGE 

II.  Photographic  equipment 500 

Making   negatives 502 

Lantern    slides 505 

Making  prints 508 

Blue  prints 510 

LIST   OF   DEALEES. 

List  of  Dealers  in  Equipment  and  Supplies 515 


ILLUSTRATIONS. 

TIG.  ■  I'AGE 

1.  Harvard   inductorium 35 

2.  DuBois-Reymond  induction  coil 36 

3.  Harvard  signal  magnet 36 

4.  Signal  magnet 36 

5.  Hale 's  signal  magnet 36 

6.  Mercury  manometer  and  signal  magnet 37 

7.  Harvard   shielded    electrodes 3S 

8.  Woulff  ether  bottle  with  regulating  clamp 38 

9.  Large  size   tracheal   cannula 39 

10.  Medium   size   tracheal   cannula 39 

11.  Small   size   tracheal   cannula 39 

12.  Mohr  pinch  cocks 40 

13.  Marey   tambour 40 

14.  Adjustable  tambour  with  three  interchangeable  bowls 40 

15.  Stethograph  drum 41 

16.  Kidney  oncometer 41 

17.  Roy's    kidney   oncometer 42 

18.  Arterial   cannula 42 

19.  Beaker 43 

20.  Dog  board  and  mouth  rod 43 

21.  Animal    board    and    head    holder 43 

22.  Small,  white  evaporating  dish 43 

23.  Glass  bladder  cannula 44 

24.  Graduated   cylinder 44 

25.  Casserole 44 

26.  Harvard   long   paper   kymograph 45 

27.  Hiirthle    long   paper    kymograph 45 

28.  Turtle    board 46 

29.  Specimen    jar 46 

30.  Burette   and   double   clamps 46 

31.  Battery  jar 47 

32.  Small    wood    tables 47 

33.  Serrefine .  48 

34.  Hemostat 48 

35.  Small  sharp-pointed  dissecting  forceps     ...         48 

36.  Scalpel 49 

37.  Small  aneurism  needle 49 

38.  Large  aneurism  needle 49 

39.  Large  blunt-pointed  dissecting  forceps 49 

40.  Small  blunt-pointed  dissecting  forceps 49 

41.  Dissecting    scissors      . 49 

42.  Dissecting  probe  (dental) 49 

43.  Large   moderately   blunt-pointed   dissecting   forceps 50 

44.  Needle  holder 50 


14  ILLUSTRATIONS 

FIG.  PAGE 

45.  Large  bottle  for  holding  stock  salt  solution 52 

46.  Frog  board   and   clip    (Harvard) 54 

47.  Dissection  of  a  frog  showing  position  of  the  brain,  sciatic  nerve  and 

arteries  and  muscles  of  the  hind  limb   (Color  plate)      ....  54 

48.  Frog's    brain 55 

49.  Method  of  pithing  a  frog 56 

50.  Harvard    moist    chamber 57 

51.  Harvard  muscle  lever 58' 

52.  Harvard  gas   chamber 58 

53.  Ether  bottles  showing  method  of  administering  air  and  ether     .     .  59 

54.  Three  forms  of  containers  for  ethyl  chloride 60 

55.  Method   of    smoking    drums 61 

56.  Automatic  shellacing  pan  and  drying  rack  for  drum  records     ...  62 

57.  Varnishing  pan  for  varnishing  records 63 

58.  Print   and   tracing   trimmer 63 

59.  Method  of  arranging  the  inductorium 64 

60.  Dissection  of  a  frog  to  show  the  position  of  the  heart,  vagus  nerve 

and  the  muscles  of  the  hind  limb  (Color  plate) 6.5 

61.  Diagrammatic  dissection  to  show  the  innervation  of  the  frog's  heart  66 

62.  Heart  lever 66 

63.  Arrangement  of  apparatus  for  recording  frog  heart  tracings     ...  67 

64.  Medicine  dropper 68 

65.  Anatomy   of   the   frog 's   heart 69 

66.  Diagrammatic  representation  of  the  lymph  spaces  of  the  frog     .     .  70' 

67.  Apparatus  for  recording  turtle  heart  tracings 72 

68.  Method  of  sawing  out  a  square  in  the  plastron  of  a  turtle     ....  73 

69.  Diagrammatic  representation  of  the  turtle's  heart   (Color  plate)      .  74 

70.  Schematic  representation  of  the   vagus   and   sympathetic  nerves  in 

a  turtle 75 

71.  Method  of  etherizing  a  dog 77 

72.  Laboratory  table 79 

73.  Metronome  for  operating  the  electric  time  signal 80 

74.  Lieb-Beeker  time  marker  made  from  an  Ingersoll  watch     ....  80 

75.  Harvard  time  clock 81 

76.  Jaquet    chronograph 82 

77.  Two  forms  of  time  clocks 82 

78.  Method  of  fastening  the  animal's  head  to  the  dog  board     ....  83 

79.  Heavy  string  with  slip  noose  ready  to  put  around  the  fore  limb     .     .  83 

80.  Method  of  attaching  fore  limbs  to  the  dog  board 84 

81.  Method  for  quickly  fastening  the  string  to  the  board  without  tying 

any  knots 84 

82.  Method  of  fastening  the  hind  limbs 85 

83.  Method  of  incising  the  skin  to  expose  the  trachea 86 

84.  Same'ks  Fig.  83.     Separation  of  borders  of  sternohyoid  muscles     .  87 

85.  Same  as  Fig.  83.     Exposing  the  trachea 87 

86.  Same  as  Fig.  83.    Lifting  up  and  passing  forceps  beneath  trachea     .  88 

87.  Same  as  Fig.  83.     Fifth  step  in  the  operation 88 

88.  Same  as  Fig.  83.     Insertion  of  the  tracheal  cannula 89 

89.  Same  as  Fig.  83.     Lifting  up  right  carotid  sheath  on  an  aneurism 

needle 89 


ILLUSTRATIONS  15 

riG.  PAGE 

90.  Same  as  Fig.  83.     Ligation  of  the  carotid  and  vago-sympathctic 

nerve 90 

91.  Same  as  Fig.  83.     Opening  the   carotid   artery 90 

92.  Same  as  Fig.  83.     Insertion  of  the  arterial  cannula 91 

93.  Same  as  Fig.  83.     Final    step   in    operation 91 

■    94.  Insertion  of  femoral  injecting  cannula 93 

95.  Dissection  to  expose  the  femoral  artery  and  vein  and  saphenous 

nerve 95 

9(3.  Same  as  Fig.  95.     Position  and  relations  of  the  vein,  artery  and 

nerve 95 

97.  Exposure  of  the  skull  for  a  trephine  opening 103 

98.  Six  inch  tinner's  snips.     For  cutting  thick  skin  and  fascia,  etc.     .  104 

99.  Same  as  Fig.  97.    Exposing  dura  mater 104 

100.  Trephine 105 

101.  Upper  surface  of  a  dog's  brain 106 

102.  "Straight"  glass  cannula .  107 

103.  Hand  bellows 107 

104.  Bandage  saw 108 

105    Method  of  opening  the  chest  by  a  median  incision 109 

106.  Method  of  exposing  the  left  pulmonary  artery  and  vein    (Color 

plate) 110 

107.  Applying  the  cardiometer  over  the  ventricles Ill 

108.  Cardiometer .112 

109.  Administration  of  nitrous  oxide  or  oxygen  to  a  frog 114 

110.  Method  for  making,  purifying  and  administering  nitrous  oxide  to 

a  frog 115 

111.  Yoke  for  tanks  of  oxygen,  nitrous  oxide  or  carbon  dioxide-    .     .     .  115 

112.  A   double  yoke   for  holding  gas   tanks 116 

113.  Yoke  for  holding  igas  tanks 116 

114.  Guthrie's   carbon   dioxide   generator 117 

115.  Method  for  studying  the  action  of  nitrous  oxide,   ethyl  chloride, 

etc.    .     .     .    '. 118 

116.  Apparatus  used  for  closed  ether  anesthesia 122 

117.  Table  arranged  for  performing  an  experiment 123 

118.  Diagrammatic  view  of  the  pan  as  seen  from  above 124 

119.  Tracing  obtained  by  the  closed  method  of  anesthesia 125 

120.  Tracing  showing  the  initial  action  of  nitrous  oxide 126 

121.  Tracing  showing  the  action  of  nitrous  oxide  and  ethyl  chloride     .  127 

122.  Apparatus  for  intratracheal  insufflation 129 

123.  Apparatus  for  administering  nitrous  oxide  to  an  animal     ....  130 

124.  Tracing  showing  action  of  carbon  dioxide 131 

125.  Injection  of  drug  solutions  into  anterior  lymph  sac  of  frog     .     .  134 

126.  Injection  of  solutions  into  anterior  lymph  sac  with  a  syringe     .  134 

127.  Injecting   pipette   made    of    glass 135 

128.  Arrangement  of  apparatus  for  recording  esoi^hageal  contractions  137 

129.  Tracing  showing  four  esophageal  contractions,  blood-pressure  and 

respiration 138 

130.  Harvard  membrane  manometer 139 

131.  Arrangement   of   apparatus   which   may   be   used   as   a   membrane 

manometer 141 


16  ILLUSTKATIONS 

FIG.  PAGE 

132.  Tracing  showing  action  of  alcohol  on  blood-pressure  and  respira- 

tion     142 

133.  Dissection  showing  vessels  and  nerves  in  the  neck  and  upper  part 

of  the  chest  in  a  dog  (Color  plate) 142 

134.  Arrangement  of  apparatus  for  recording  reaction  time  for  sight     .  143 

135.  Simple   key 145 

136.  Electric  tuning  fork 145 

137.  Apparatus  for  recording  reaction  time  for  hearing 146 

138.  Box  for   anesthetizing   cats 147 

139.  Bell-jar  as  used  for  anesthetizing  cats 148 

140.  Glass  or  earthen  ware  jar  covered  by  a  glass  plate 148 

141.  Myocardiograph 149 

142.  Cardiometer  arranged  for  use  as  a  myocardiograph 150 

143.  Cardiometer  made  from  a  large  thistle  tube 151 

.144.  Arrangement  of  apj)aratus  for  recording  heart  tracings     ....  152 

145.  Special  heart  holder 153 

146.  Heart   levers   for   dogs 154 

147.  Schematic  representation  of  the  innervation  of  the  heart   (Color 

plate) 154 

148.  Innervation  of  heart  in  the  cat 155 

149.  Myocardiographic  and  blood-pressure  tracings  from  a  dog     .     .     .  156 

150.  Fermentation   tube        157 

151.  Apparatus  for  recording  the  pressure  of  the  cerebrospinal  fluid     .  159 

152.  Spleen  oncometer  for  dogs 160 

153.  Spleen  oncometer  for  dogs 161 

154.  Kidney  oncometer 162 

155.  Rear  view  of  same  oncometer  shown  in  Fig.  154 162 

156.  Kidney  oncometer  made  of  a  metal  pill  or  ointment  box     ....  163 

157.  View  showing  the  oncometer  partly  open 163 

158.  Dissection  exposing  the  kidney  from  a  median  incision     ....  164 

159.  Arrangement   of   apparatus   for  making   several   records   simulta- 

neously         165 

160.  Appearance   of   the   blood-vessels   in   the   ears   of   a   white   rabbit 

(Color   plate) 166 

161.  Dissection  showing  position  of  left  pulmonary  vessels  and  sympa- 

thetic trunk  in  chest  above  diaphragm  (Color  plate)     ....  166 

162.  Dissection  to  show  the  abdominal  viscera  (dog) 167 

163.  Electric   ophthalmoscope 170 

164.  Method  used  for  observing  the  retinal  circulation  in  a  frog     .     .     .  171 

165.  Ventral  and  dorsal  views  of  a  pigeon's  brain 173 

166.  Posterior  view  of  the  bi'ain  and  semicircular  canals  of  a  pigeon     .  174 

167.  Lateral  view  of  head  of  pigeon  showing  brain,  etc 174 

168.  Base  of  the  brain  of  a  dog 175 

169.  Upper  surface  of  the  skull  of  a  cat 178 

170.  Mesial  section  showing  the  left  half  of  the  interior  of  a  cat's  skull  179 

171.  Dorsal   surface   of  the  brain   of   a   cat 180 

172.  Apparatus  for  recording  and  measuring  the  rate  of  oxygen  con- 

sumption      181 

173.  Inner  construction  of  the  pans  shown  in  Fig.  172 182 

174.  Lateral  view  of  a  cross-section  of  the  apparatus  shown  in  Fig.  172  182 


ILLUSTRATIONS  17 

FIG.  PAGE 

175.  Arrangement  for  recording  oxygen  consumption  by  an   animal     .  1S3 

176.  Apparatus  used  for  making  pure  oxygen 185 

177.  Gas  reservoir  made  from  a  very  shallow,  wide,  round  cake  pan     .  180 

178.  Dreser's  apparatus  for  respiratory  measurements 187 

179.  Teclinic  for  inserting  a  bladder   cannula 188 

180.  Tracing  showing  action  of  morphine  on  oxygen  consumption     .     .  191 

181.  Eecord  showing  the  action  of  adrenaline  on  the  rate   of  oxygen 

consumption,  uterine  contractions,  blood-pressure  and  respira- 
tion     192 

182.  Schematic  representation  of  the  course  of  the  right  phrenic  nerve 

in  a  dog 193 

183.  D.issection  of  lower  part  of  neck  and  upper  part  of  chest  on  right 

side  in  dog   (Color  plate) 194 

184.  Dissection  of  lower  part  of  neck  and  upper  part  of  chest  and  of 

axillary  region  in  dog   (Color  plate) 194 

185.  Large  needles  for  sewing  with  heavy  twine 195 

186.  Brass  tube  with  spear  point     . 196 

187.  Arrangement  of  animal  for  recording  lung  volume  changes     .     .     .  196 

188.  Apparatus  for  keeping   the   systematic   blood-pressure   at    a   con- 

stant level 197 

189.  Lung  volume   and   blood-pressure    record 198 

190.  Tracings  showing  the  action  of  morphine 199 

191.  Tracings  showing  the  action  of  pantopon 200 

192.  Tracings  showing  the  action  of  peronine 201 

193.  Tradings  showing  the  action  of  dionine 202 

194.  Tracings  showing  the  action  of  narcotine 203 

195.  Tracings  showing  the  progressive  actions  of  narcophine,  narcotine 

and  morphine 204 

196.  Method  of  administering  capsules,  pills  or  tablets  to  dogs     .     .  205 

197.  Merctry    bulb 206 

198.  Apparatus  for  recording  bladder  contractions 207 

199.  Same  as  Fig.   198.     Dissection  for  the  femoral  vessels     ....  208 

200.  Lung  shield  made  of  thin  sheet  brass 209 

201.  Method  of  recording  volume  changes  of  the  lung  by  use  of  the 

lung  shield 210 

202.  Tracing  showing  action  of  heroine    and    adrenaline 212 

203.  Tracing  showing  the  action  of  codeine   and   epinine 213 

204.  Tracing  showing  the  action  of  muscarine 214 

205.  Tracing  showing  the  action  of  codeine  on  turtle 's   lungs     .     .     .  215 

206.  Three  kinds   of  catheters 216 

207.  Dissection  of  the  pelvis  of  dog 216 

20S.  Arrangement  of  apparatus  for  recording  convulsions  in  a  frog     .  218 

209.  Tracing  showing  the  action  of  strychnine 219 

210.  Greene's  method  of  irrigating  the  heart 221 

211.  Tracing  showing  the  action  of  strychnine  on  the  turtle's  heart     .  222 

212.  Glass  oncometer  for  a  small  loop  of  the  intestine 223 

213.  Glass  ureteral  cannula  Avith  rubber  tube  connection 225 

214.  Tracing  showing  the  action   of  morphine 228 

215.  Tracings   showing  the  action  of  picrotoxine 232 

216.  Tracings  showing  the  action  of  brucine 233 


18  ILLUSTEATIOI^S 

FIG.  PAGE 

217.  ]V[etliod  of  administering  medicine  to  a  dog  by  means  of  the  stom- 

ach tube ,     .     .     .  234 

218.  Mouth  gag  for  dogs,  cats  or  rabbits 235 

219.  Dissection  to  expose  the   sciatic  nerve 237 

220.  Method  of  destroying  the  cerebrum  only  in  a  frog 238 

221.  Tracing  showing  action   of  hydrastine 239 

222.  Innervation  of  the  heart  in  the  frog  or  turtle 240 

223.  Tracing   showing   the    action   of   arecoline,    hydrastinine    and   ad- 

renaline        242 

224.  Arrangement  of  a  frog  and  ajjparatus  for  recording  fatigue  trac- 

ings     245 

225.  Showing  a  method  for  making  cannulas  with  separable  point-s     .     .  246 

226.  Structures  in  the  neck  of  a  rabbit  showing  the  arrangement  of  the 

nerves  on  the  left  side   (Color  plate) 247 

227.  Glass  cannula  showing  a  special  washout  opening 248 

228.  Arrangement  of  two  tambours  to  form  a  drop  recorder     ....  250 

229.  Tracing  showing  action  of  sodium  sulphate 251 

230.  Tracing  showing  the   action   of   curara 256 

231.  Innervation  of  the  salivary  glands  in  the  dog  (Color  plate)     .     .  257 

232.  A  turtle  prepared  for  recording  lung  tracings 261 

233.  Arrangement  of  apparatus  for  recording  lung  contractions     .     .     .  262 

234.  Lung  tracing  from  a  turtle 263 

235.  Lung  and  heart  tracings  from  a  turtle 264 

236.  Diagrammatic  representation  of  innervation  of  lachrymal  glands  265 

237.  First  incision  for  exposing  the  chorda  tympani  nerve,  etc.     .     .     .  266 

238.  Dissection  showing  position  and  relation  of  hypoglossal  and  lin- 

gual  nerves    (Color   plate) 266 

239.  Exposure  of  the  ling-ual  and  hypoglossal  nerves  and  salivary  ducts 

(Color  plate) 266 

240.  Exposure  of  the  chorda  tympani  nerve    (Color  plate)     ....  266 

241.  Tracing  showing  the  action  of  pilocarpine 274 

242.  General  course  of  the  nerves  to  the  salivary  glands  (Color  plate)  274 

243.  The    submaxillary   and    sublingual    glands    and    their    ducts,    etc. 

(Color  plate) 274 

244.  A  dissection  showing  position  and  relations  of  pancreatic  ducts  in 

dog 276 

245.  Position    and    relations    and    method    of    isolating   large    duct    of 

pancreas  in  dog  (Color  plate) 278 

246.  Arrangement  of  apparatus  for  recording  contractions  of  intestine.  279 

247.  Tracing  showing  the  action  of  barium,  adrenaline  and  atropine     .  280 

248.  Tracing  showing  action  of  barium  and  adrenaline 281 

249.  Tracing  showing  the  action  of  arecoline  and  of  atropine      .     .     .  282 

250.  Innervation  of  the  retractor  penis  muscle  (Color  plate)     ....  282 

251.  Tracing  showing  the  action  of  pilocarpine 283 

252.  Tracing  showing  the  action  of  a  fatal  dose  of  barium  chloride     .  284 

253.  Tracing  showing  the  action  of  adrenaline  and  barium  chloride     .  285 

254.  Tracing  showing  the  action  of  a  fatal  dose  of  barium  chloride     .  286 

255.  A  form  of  apparatus  used  in  recording  lung  tracings 288 

256.  A  form  of  apparatus  used  in  recording  lung  tracings     ....  289 


ILLUSTRATIONS  19 

FIG.  PAGE 

257.  Adjustment  of  the  apparatus  shown  in  Fig.  25.5  in   the  chest  of 

a  dog 290 

258.  Method  of  making  the  first  incision  before  trephining  tlie  skull     .  292 

259.  The    trephine    opening 292 

260.  Method  of  quickly  cutting  across  the  brain  stem 293 

261.  Method   of    destroying   the   brain 293 

262.  Plugging  trephine  opening  with  cotton  after  brain  is  destroyed  .  294 
263A.  Tracing  showing  the  action  of  pilocarpine  and  atropine  .  .  .  295 
263B.  Tracing  showing  the  action  of  muscarine  and  atropine     ....  295 

264.  Tracing  showing  the  action  of  lodal 296 

265.  Tracing  showing  the  action  of  arecoline 298 

266.  Tracing  showing  the  action  of  arecoline  and  atropine      ....  299 

267.  Tracing  showing  the  action  of  nicotine 301 

268.  Tracing  showing  the  action  of  nicotine 303 

269.  Method  of  applying  a  plethsmograph  to  the  hind  leg  of  a  dog     .  304 

270.  Tracing  showing  the  action  of  a  fatal  dose  of  nicotine     ....  305 

271.  Arrangement   of   apparatus  for  recording  intraocular  pressure     .  308 

272.  Tracing  showing  the  action  of  nicotine 309 

273.  Arrangement  of  apparatus  for  recording  pulmonary  blood-pressure  311 

274.  Dissection   showing   the   method    of   ligating   the  left   pulmonary 

artery 312 

275.  Second  step  in  preparing  to  insert  a  cannula  in  the  pulmonary 

artery 312 

276.  Third   step   in   preparing   to   insert   a   cannula   in   the   pulmonary 

artery 313 

277.  Method  of  inserting  the  special  cannula  iiito  the  artery     ....  313 

278.  Special  form  of  separable  pointed  cannula  for  pulmonary  artery     .  315 

279.  Special  (all-glass)  form  of  cannula  for  the  pulmonary  artery     .     .  315 

280.  Tracing  showing  the  action  of  adrenaline 317 

281.  Method  of  dissecting  out  the  orbital  fat  and  fascia  to  expose  the 

optic  nerve 319 

282.  Bone  cutting  forceps 320 

283.  Tracing  showing  the  action  of  lobeline,  arecoline  and  atropine     .  323 

284.  Tracing  showing  the  action  of  lobeline 324 

285.  Tracing  showdng  the  action  of  lobeline 324 

286.  Tracing  showing  the  action  of  pilocarpine 325 

287.  Tracing  showing  the  action  of  lobeline .  326 

288.  Tracing  showing  the  action  of  lobeline 327 

289.  Tracing  showing  the  action  of  tetramethylammonium   chloride     .  329 

290.  Tracing  shownng  the  action  of  tetramethylammonium   chloride     .  330 

291.  Tracing   showing  the   action   of  pilocarpine,    and   tetramethylam- 

monium chloride 331 

292.  Arrangement    of    apparatus    for    recording    contractions    from    a 

uterine  strip,  or  from  an  arterial  ring,  ureter  ring,  intestinal 

strip,  ring  of  frog's  stomach,   etc. 333 

293.  Tracing  showing  the  action  of  muscarine 335 

294.  Diagrammatic  cross-section  of  the  intestine   (Color  plate)     .     .     .  336 

295.  Tracing  showing  the  action  of  nicotine,  arecoline  and  atropine     .  336 

296.  Tracing  showing  the  action  of  trimethylamine 340 

297.  Tracing  showing  the  action  of  pilocarpine  and  trimethylamine     .  341 


20  ILLUSTRATIOIsTS 

FIG.  Px'^GE 

298.  Arrangement  of  apparatus  for  perfusion  of  an  excised  organ     .     .  343 

299.  Tracings  showing  action  of  sodium  orthovanadate,  barium   chlo- 

ride,   and    adrenaline 345 

SOOt.  Tracing  showing  the  action  of  heroine  and  adrenaline     ....  348 

301.  Tracing   showing   effects   of   cocaine 352 

302.  Method  of  exposing  the  lymphatic  ducts  and  connecting  cannulas 

to  collect  the  lymph  or  chyle  (Color  plate) 356 

303.  Metallic  muzzle  for  administering  an  anesthetic  to  a  dog     .     .     .  357 

304.  View  of  the  reverse  side  of  the  metallic  muzzle  shown  in  Fig.  303  358 

305.  Arrangement  of  apparatus  for  observing  the  capillary  circulation  362 

306.  Arrangement  of  animal  and  apparatus  for  recording  uterine  con- 

tractions       364 

307.  Tracing  showing  the  action  of  barium  chloride 365 

308.  Tracing  showing  the  action  of  ergamine  (histamine)  and  adrena- 

line     "  . 307 

309.  Tracing  showing  the  action  of  ergamine 368 

310.  Tracing  showing  the  action  of  tyramine 370 

311.  Tracing  showing  the  action  of  adrenaline  and  ergamine      .     .     .  372 

312.  Tracing  showing  the  action  of  ergamine  and  hordenine     .     .     .     .  376 

313.  Tracing  showing  the  action  in  succession  of  arecoline,  lodal,  the- 

baine,  lodal,  hordenine  and  adrenaline 377 

314.  Tracing  showing  the  consecutive  actions  of  ergotoxine  phosphate, 

pilocarpine,   (ergotoxine)  and  adrenaline 378 

315.  Tracing  showing  the  action  of  areeoline,  ergotoxine,    farecoline) 

and    adrenaline 379 

316.  Arrangement  of  apparatus  for  recording  contractions  of  a  uterine 

strip,   intestinal   strip,   etc 381 

317.  Arrangement  of  apparatus  for  recording  contractions  of  the  uterus 

in   situ 382 

318.  Schematic  representation  of  the  involuntarj^  nervous  system  (Color 

plate) 384 

319.  Method   of  isolating  the  thoracic   duct   at   the  root   of   the   neck 

(Color  plate) .  384 

320.  Diagrammatic  representation  of  the!  lymphatic  system  in  a  cat     .  386 

321.  Tracing   showing  the   action   of   pituitrin 388 

322.  Tracing   showing  the   action   of   pituitrin 389 

323.  Tracing   showing  the   action   of   pituitrin 391 

324.  Schematic   representation   of  the   innervation   of   the    eye    (Color 

plate 394 

325.  Diagrammatic  representation  of  the  structure  and  innervation  of 

the  eye  (Color  plate) 394 

326.  Plethysmograph  for  recording  volume  changes  in  hand  and  fore- 

arm   398 

327.  Dudgeon's   sphygmograph   arranged   for   recording   tracings   from 

the  radial  pulse 399 

328.  Tracing  showing  action  of  amylnitrite 400 

329.  Tracing  showing  the  action  of  nitroglycerine        405 

330.  Tracing  showing  the  action  of  digitoxin 409 

331.  Tracing  showing  the  action  of  digitoxin 410 

332.  Tracing  showing  the  action  of  digitoxin 411 


ILLUSTRATIONS  21 

FIG.  PAGE 

333.  Tracing  showing  tho  action  of  cligitoxin 412 

334.  Tracing  showing  the  final  result  of  the  action   of  digitoxin     .     .  413 

335.  Illustration   showing   principles   involved   in   construction   of   Ed- 

munds'  liver    oncometer 416 

336.  Tracing  showing  the  action  of  adrenaline 417 

337.  Spleen  oncometer  made  of  crimped  sheet  brass 421 

338.  Liver   oncometer 422 

339.  Tracing  showing  the  action  of  tetramethylammonium  chloride     .  423 

340.  Arrangement  of  apparatus  for  recording  tracings  from  an  excised 

heart 425 

341.  Cat's   heart 426 

342.  Dog's  heart 427 

343.  Tracing  showing  the  linal  action  of  aconitinc 432 

344.  Tracing  showing  the  action  of  veratrine       ..........  435 

345.  Arrangement  of  apparatus  for  spinning  a  drum 436 

346.  Tracing  showing  the  action  of  veratrine 438 

347.  Tracing  showing  the  action  of  sodium  cyanide 442 

348.  Tracing  showdng  the  action  of  potassium  cyanide 443 

349.  Tracing  showdng  the  action  of  sodium  cyanide 444 

350.  Tracings  showing  the  action  of  dilute  sodium  cyanide  solution     .  445 

351.  Tracing  showing  the  action  of  pilocarpine  and  (3-tetrahydronaph- 

thylamine  hydrochloride 450 

352.  Two  tracings  showing  the  action  of  a  drug  which  markedly  lowers 

blood-pressure 455 

353.  Arrangement  of  apparatus  for  perfusion  of  the  vessels  of  a  brain- 

less frog 459 

354.  Tracing  showing  the  action  of  adrenaline  sodium  orthovanadate, 

amylnitrite  and  adrenaline 463 

355.  Tracing  showing  the  action  of  vanadium 464 

356.  Tracing  showing  the  action  of  vanadium 465' 

357.  Arrangement   of   the   ligatures   for   isolating  segments   of   the   in- 

testine   467' 

358.  A  schematic  representation  of  an  electric  wiring  system     ....  471 

359.  Foot  bellows    . 472^ 

360.  Diagrammatic  representation  of  an  artificial  respiration  machine  473'' 

361.  View  of  system  of  pulleys  used  to  operate  the  interrupting  valve  474 

362.  Lever  gate  valve 474 

363.  Diagram   showing   method   of   operation   of  lever   gate   reversing 

valves 475 

364.  Portable   artificial  respiration  machine 475 

365.  Special  form   of  interrupting  valve 476 

366.  Special  interrupting  valve 477 

367.  A  motor  driven  long  paper  kymograph 478 

368.  Detailed  view  of  one  plan  of  construction  of  the  speed  regulating- 

device   for   the   kymograjDh 479 

369.  Motor  driven  long  paper  kymograph 480 

370.  Hand   drill       481 

371.  Blast  lamp 482 

372.  Details  of  the  mechanical  construction  of  an  adjustable  tambour  483 

373.  A  large   bowled   tambour 484 


22  ILLUSTRATIONS 

FIG.  PAGE 

374.  Method  of  tying  head  of  a  small  screw  into  rubber  niembrane     .  484 

375.  Some  of  the  more  common  types  of  gas  pipe  fittings 486 

376.  Small  electric  heater 487 

377.  Method    of   preparing   two    pieces    of    brass    tnbing    for    making 

a  tracheal  cannula 490 

378.  Method  of  making  "straight"  glass  cannulas 492 

379.  Same  as  Fig.  378 492 

378     ........ 492 

381.  Same  as  Fig.  378 494 

382.  Same  as  Fig.  378 .  494 

making  frog  clips 495 

making  very  small  brass  cannulas     .......  496 

385.  Large   stand   with  L-shaped  base ;     .     .  497 

386.  Method  of  arranging  the  camera  and.  arc  light  for  copying     .     .  501 

387.  Method  of  suspending  an  adjustable  are  light  above  the  operating 

table 502 

388.  Measuring   glass 504 

389.  Adjustable  frame  for  cutting  lantern   slide  mats 507 

390.  Frame  for  making  blue  prints 511 


383.  Process  for 

384.  Method  for 


INTRODUCTION. 

The  unit  of  procedure  adopted  in  this  manual  is  the  ex- 
periment. Each  experiment  is,  as  a  rule,  complete  within 
itself,  although  in  many  instances  an  orderly  sequence  pro- 
ceeding from  the  simple  to  the  more  complex,  from  the 
known  to  the  unknown,  has  been  introduced.  The  writer 
has  at  all  times  tried  to  hold  in  mind  the  fact  that  the  in- 
structor is  not  only  teaching  i)harmacology  but  that  he  is 
also  teaching  medical  students.  And  the  mental  and  tech- 
nical abilities  and  limitations  of  these  students  are  quite 
as  significant  from  the  standpoint  of  the  teacher  as  is  the 
wide  extent,  the  complexity,  and  the  importance  of  the  sub- 
ject which  he  practically  invariably  has  a  too  limited  time 
to  cover.  It  is  constantly  necessary  for  the  teacher  of 
pharmacology  to  bear  in  mind  that  the  knowledge  which 
his  students  possess  of  the  fundamental  principles  of  anat- 
omy, neurology,  physiological  chemistry,  pathology,  and 
especially  of  physiology,  is  by  no  means  complete,  and  much 
of  the  instructor's  time  must  of  necessity  be  consumed  in 
again  bringing  to  the  attention  of  the  students  fundamental 
and  often  exceedingly  elementary  facts  invoh^ed  in  the 
nature  of  subjects  prerequisite  to  the  course  in  pharma- 
cology. And  it  will  not  infrequently  severely  tax  the  in- 
genuity of  the  teacher  of  pharmacology  to  determine  by 
what  means  he  can,  within  a  brief  period  of  time,  best 
recall  to  the  student's  mind  some  fundamental  princij)les, 
e.  g.,  of  iDhysiology  or  neurology,  without  a  knowledge  of 
which  further  progress  in  pharmacology  is  totally  impos- 
sible. The  author  has  kept  these  points  carefully  in  mind 
in  preparing  this  manual,  and  many  of  the  exjDeriments, 
illustrations  and  tracings  have  been  introduced  quite  as 
much  with  the  object  of  teaching  certain  fundamental  prin- 


24  IJ^TRODUCTIOIS;" 

ciples  of  anatomy,  chemistry,  physiology,  etc.,  as  for  their 
immediate  use  in  the  work  on  pharmacology. 

It  has  been  the  author's  aim  to  try  to  develop  experimen- 
tally a  knowledge  of  the  general  principles  of  pharmacolog- 
ical reactions,  rather  than  to  lay  great  emphasis  on  a  vast 
array  of  details  regarding  the  specific  action  of  a  long  list  of 
substances.  There  are  more  than  100,000  known  organic 
preparations,  with  many  more  theoretically  possible.  In  ad- 
dition to  this  there  are  some  3,000  or  4,000  inorganic  sub- 
stances, salts,  etc.  A  very  large  proportion  of  these  bodies 
might  be  studied  separately  and  individually  so  far  as  their 
pharmacological  properties  and  reactions  are  concerned. 
And  if  we  attempt  to  have  our  students  make  a  fairly  in- 
tensive study  of  only  the  one-thousandth  part  of  all  this 
vast  array  of  chemical  substances,  the  task  is  still  so  great 
that  perhaps  no  human  mind  can  grasp  and  carry  within 
the  memory  at  any  one  time  the  almost  limitless  extent  of 
the  specific  details  of  the  pharmacological  reactions  of 
which  even  this  comparatively  small  number  of  drugs  may 
theoretically  be  caj)able.  And  notwithstanding  the  more 
or  less  abortive  attempts  of  nearly  all  recent  writers  and 
examining  boards,  to  limit  as  far  as  possible  the  number  of 
drugs  which  the  student  must  study,  the  task  of  selection  is 
still  largely  one  for  the  individual  instructor. 

The  experiments  listed  herein  are,  as  a  rule,  arranged 
with  reference  to  individual  drugs.  The  simplest  and 
easiest  experiments  on  any  given  substance  are  usually 
placed  at  the  beginning  of  the  section  dealing  with  that 
body.  Being  keenly  aware  of  the  difficulty  often  experi- 
enced in  obtaining  suitable  experimental  material  the 
author  has  included  a  large  number  of  experiments  on  frogs 
and  turtles,  the  supply  of  Avhich  is  less  liable  to  variation 
than  is  that  of  the  vastly  more  desirable  mammalian  ma- 
terial. Generally  a  number  of  experiments  are  given  on 
each  drug,  especially  if  it  be  one  of  importance.  It  is  in- 
tended that  these  experiments  be  assigned  to  the  students 


INTEODUCTION"  25 

on  the  day  before  the  experiment  is  to  be  performed  in  order 
that  each  member  of  the  class  may  familiarize  himself  with 
the  work  he  is  expected  to  do.  Many  of  the  experiments 
may  be  done  as  demonstrations.  It  is  usually  advisable  for 
each  group  to  do  a  different  experiment  at  any  given  labora- 
tory period.  This  economizes  on  the  amount  of  special 
apparatus  required  and  also  furnishes  an  opportunity  for 
each  group  of  students  to  compare  its  results  with  those 
obtained  by  the  other  groups.  This  arrangement  also  gives 
an  opportunity  for  the  instructor  to  devote  most  attention 
to  those  experiments  where  help  is  most  needed. 

The  general  anesthetics,  being  of  fundamental  impor- 
tance for  the  progress  of  the  course,  are  taken  up  first. 
Following  this  is  a  group  of  drugs  chiefly  characterized  by 
their  action  on  the  central  nervous  system.  After  these 
come  a  series  of  substances  possessing  specific  actions  on 
some  one  or  more  parts  of  the  involuntary  nervous  system. 
These  are  followed  by  drugs  which  act  mainly  on  the  cir- 
culatory system,  then  follow  the  antipyretics,  a  few  mis- 
cellaneous drugs,  and  finally  a  few  experiments  on  acids, 
alkalies,  and  some  of  the  heavy  metals. 

The  second  part  of  the  book  contains  two  chapters,  one 
on  shop  Avork  and  one  on  i^hotography.  These  are  chiefly 
of  interest  to  the  instructor,  and  it  is  advised  that  these  be 
read  in  connection  with  the  general  preparation  of  appa- 
ratus, equipment,  etc.,  for  the  course  in  pharmacology. 

Any  general  text  book  on  the  subject  of  pharmacology 
may  be  used  in  connection  with  this  manual,  or  if  the  in- 
structor prefers  to  deliver  a  course  of  set  lectures  on  the 
general  field  of  pharmacology,  no  didactic  text  at  all  may 
be  required.  That  is  a  matter  for  each  teacher  to  decide 
for  himself. 

Usually  drugs  are  taken  up  one  at  a  time.  It  is  desir- 
able not  to  confuse  the  student  more  than  can  be  helped 
by  the  introduction  of  too  many  drugs,  especially  if  the 
actions  of  the  drugs  involve  general  pharmacological  iDrin- 


26  INTRODUCTIOISr 

ciples  with  which  the  student  is  unfamiliar.  It  often  oc- 
curs, however,  that  as  the  student  gains  in  experience  and 
in  technical  ability,  drugs  which  have  already  been  studied 
may  be  reintroduced  either  as  a  matter  of  review,  or  to 
demonstrate  certain  actions  of  other  drugs  which  are  not 
•evident  until  brought  to  light  by  the  changed  response  of 
certain  structures  to  drugs  injected  secondarily,  or  to  serve 
■SiS  a  check  on  the  action  of  the  apparatus  and  the  general 
technic  employed  in  the  experiment.  For  this  latter  pur- 
pose great  use  is  made  of  adrenaline  in  these  experiments. 
This  often  serves  the  double  purpose  of  reviving  an  animal 
Avhen  it  is  in  a  very  feeble  condition,  and  also  gives  the 
■student  {and  instructor)  an  immediate  indication  of  the 
accurary  of  the  working  of  his  apparatus  and  of  the  condi- 
tion of  the  animal.  It  should  be  especially  emphasized  that 
the  extensive  use  made  of  adrenaline  in  many  of  the  ex- 
periments is  solety  for  the  purposes  here  indicated,  and  its 
frequent  injection  should  not  be  considered  in  any  sense  as 
--a  useless  repetition  of  the  same  experiment. 

It  is  imperative  to  use  the  strictest  economy  Avith  the  ex- 
perimental material.  For  this  reason  it  is  desirable  for 
the  students  to  learn  everything  possible  from  each  animal 
used.  Consequently  many  experiments  are  listed  here  in 
ivliich  a  variety  of  reactions  may  be  recorded  at  the  same 
time.  The  instructor  should  use  his  judgment  in  the  case 
of  each  group  of  students  regarding  the  number  of  records 
which  the  group  will  probably  l)e  able  to  successfully  se- 
cure. And  he  should  not  hesitate  to  eliminate  any  indicated 
part  of  the  experiment  in  which  he  believes  the  group  will 
fail.  The  author  has,  however,  often  been  amazed  at  the 
excellent  success  which  students  with  some  experience  may 
frequently  obtain  in  carrying  out  exceedingly  difficult  and 
involved  experiments.  And  the  writer  recommends  that 
the  instructor  should  not  hesitate  to  permit  a  group  of 
students  to  attempt  to  carry  out  a  difficult  experiment 
^whenever  he  can  advisedly  do  so.  For  it  should  be  espe- 
cially emphasized  that  a  student's  own  failure  may  be  of 


IJSTTRODUCTION"  27 

vastly  more  interest  and  value  to  him  than  would  he  a  per- 
fect success  of  that  same  experiment  demonstrated  by  the 
instructor  or  his  assistants. 

Many  instructors  advise  that  each  student  in  the  group 
take  his  turn  at  doing  various  jiortions  of  the  routine  work. 
In  the  writer's  opinion  this  will  probably  not  be  the  most 
valuable  line  of  procedure  in  the  long  run.  For  while  it 
may  be  very  desirable  for  each  student  to  acquire  a  certain 
amount  of  skill  in  performing  each  part  of  the  experiment 
(and  students  usually  want  to  do  this  at  the  start)  the  fact 
remains  that  the  total  time  devoted  to  the  subject  is  too 
short  for  any  student  to  become  an  expert  in  carrying  out 
all  phases  of  the  work.  It  will  yield  a  greater  percentage 
of  pharmacological  successes  for  each  student  to  learn  a 
given  portion  of  the  routine  work  well  and  to  faithfully 
carry  this  out  for  each  experiment.  It  should  be  empha- 
sized that  the  chief  object  of  the  experimental  course  is  not 
to  teach  surgery,  but  pharmacology.  For  while  students 
may,  and  in  a  thoroughly  satisfactory  course  perhaps  do, 
acquire  a  very  fair  amount  of  the  knowledge  of  surgery 
which  they  Avill  later  possess,  this  should  be  looked  upon 
solely  as  a  matter  of  secondary  imjoortance. 

Practice  dissections  on  dead  animals  are  frequently  de- 
scribed at  the  end  of  experiments.  This  is  a  matter  of 
great  importance  and  the  instructor  can  often  be  of  much 
help  to  the  student  by  aiding  in  this  work  to  see  that  it  is 
properly  done.  These  dissections  usually  precede  experi- 
ments in  which  the  dissected  structures  will  be  concerned. 

A  few  Avords  may  be  said  about  the  matter  of  dosage. 
T^his  is  a  difficult  subject  and  the  writer  has  been  compelled 
to  depend  mainly  on  his  own  records  and  experience  in  this 
line,  for  most  of  the  published  dose  tables,  etc.,  are  based 
on  quantities  of  the  drugs  to  be  given  by  mouth.  A  further 
difficulty  arises  from  the  great  variation  in  the  size  and  re- 
sistance of  different  animals,  and  from  the  variation  in 
potency  of  the  different  drugs  as  purchased  in  the  open 


28  INTEODUCTIO:?^ 

market.  The  instructor  is  advised  to  make  all  the  observa- 
tions he  can  on  this  subject  for  the  benefit  of  his  students. 

One  of  the  most  valuable  things  which  a  course  in  ex- 
perimental pharmacology  can  offer  to  a  student  is  the  very 
great  opportunity  which  is  presented  to  develop  his  power 
to  think,  to  observe,  and  to  learn  at  first  hand  for  himself. 
In  nearly  all  of  the  experim.ents  questions  are  asked  which 
are  intended  to  direct  his  attention  to  the  most  vital  and 
important  features  of  the  work,  and  to  encourage  him  to 
test  out  experimentally  the  truth  or  falsity  of  his  own 
conclusions. 

Every  student  of  modern  medicine  must  have  been  im- 
pressed at  some  time  in  his  Avork  by  the  very  great  aid 
which  he  has  derived  in  his  study  of  anatomy  or  neurology 
or  operative  surgery  from  the  use  of  illustrations,  dia- 
grams, etc.  These  are  frequently  of  the  greatest  use  for 
rapidly  reviewing  work  over  which  one  has  long  since 
passed,  or  for  quickly  advancing  one 's  knowledge  into  fields 
with  which  he  may  be  less  familiar.  The  author  has  care- 
fully considered  this  phase  of  the  subject  in  writing  the 
present  manual.  And  numerous  illustrations,  tracings,  dia- 
grams, etc.,  have  been  devised  and  presented  with  the  spe- 
cial object  of  enabling  the  student,  teacher  or  practitioner 
of  medicine  to  quickly  and  accurately  grasp  the  full  mean- 
ing and  significance  of  important  actions  of  the  drugs  con- 
sidered. To  one  who  already  possesses  a  moderate  famil- 
iarity with  the  subject  of  modern  pharmacology,  a  brief 
glance  at  the  nature  of  mau}^  of  the  experiments  presented, 
together  with  a  rapid  study  of  the  accompanying  tracings, 
may  reveal  the  character  and  results  of  the  effects  which 
follow  the  application  of  drugs  to  the  animal  organism  with 
a  vividness  Avhieh  can  be  exceeded  only  by  the  knoAvledge 
acquired  by  the  actual  performance  of  the  experiments 
themselves. 

Finally  it  may  be  stated  that  originality  and  individu- 
ality, not  only  for  the  student  but  for  the  instructor  as  well. 


INTEODUCTIOlSr  29 

should  be  encouraged  in  every  way  possible.  For  experi- 
mental pharmacology  covers  a  wide  range,  and  there  is  at 
present  perhaps  no  phase  of  the  whole  field  of  medicine 
which  promises  more  for  the  future  alleviation  of  human 
suffering  than  does  this,  in  a  sense  one  of  the  oldest,  and 
yet  one  of  the  newest  of  all  the  divisions  of  medical  science. 


A  NOTE  TO  THE  STUDENT. 

When  pursued  under  satisfactory  conditions  experi- 
mental pharmacology  is  one  of  the  most  valuable  and  in- 
teresting of  all  medical  subjects.  The  province  of  this 
AVork  is  comparatively  new,  and  unfortunately  so  far  as 
the  medical  student  is  concerned,  is  but  poorly  developed. 
The  student,  as  well  as  his  teacher,  will  feel  these  limita- 
tions mainly  in  the  lack  of  suitable  apparatus  and  perhaps 
in  many  cases  in  a  lack  of  sufficient  experimental  materiaL 
The  apparatus  as  a  rule  is  very  expensive  and  usually  is 
obtained  only  with  considerable  difficulty,  while  in  a  large 
number  of  instances  equipment  suitable  for  the  perform- 
ance of  many  of  the  most  valuable  and  interesting  experi- 
ments must  be  made  up  according  to  special  directions. 
From  this  it  is  perfectly  obvious  that  no  two  schools  can 
expect  to  possess  exactly  the  same  kind  of  apparatus  for 
the  performance  of  any  given  series  of  experiments.  The 
student  will  often  find  it  necessary  to  carry  out  his  work 
with  apparatus  entirely  different  from  that  described  in 
the  text  and  often  perhaps  with  an  equipment  which  is 
exceedingly  unsatisfactory.  He  should  by  no  means  be 
discouraged  thereby,  for  much  of  the  most  valuable  ex- 
perimental work  of  all  history  has  been  performed  with 
crude  and  unwieldy  apparatus,  and  often  under  most  dis- 
couraging circumstances.  To  accomplish  much  A\dth  little 
is  a  sure  sign  of  ability  and  the  medical  student  who  ap- 
proaches the  subject  of  experimental  pharmacology  at  the 
present  time  Avill  find  numerous  opportunities  to  demon- 
strate his  aptitude  in  this  direction.  He  should  seize  these 
opportunities  Avith  keenness  and  alertness  and  with  a  full 
appreciation  of  the  advantage  which  he  possesses  over 
that  of  the  medical  student  who  may  have  been  taught  ex- 
perimental pharmacology  some  ten  or  fifteen  years  ago. 


32  A   NOTE    TO    THE    STUDENT 

Each  experiment  in  this  book  Avas  designed  primarily  to 
give  the  student  an  opportunity  to  learn  to  think,  and  sec- 
ondarily to  teach  him  some  valuable  point  in  connection 
with  the  drugs  studied.  The  writer  full}^  appreciates  that 
there  are  certain  difficulties  and  limitations  beyond  which 
the  average  medical  student  can  not  go,  and  for  the  satis- 
factory performance  of  the  following  experiments  there 
has  been  assumed  a  certain  standard  of  attainment  which 
to  the  author's  mind  represents  approximately  that  de- 
gree of  training  which  the  average  sophomore  student  at 
the  present  time  should  have  had  when  he  takes  up  the 
study  of  experimental  pharmacology.  The  student  mil  feel 
constantly  the  necessity  of  drawing  extensively  upon  his 
knowledge  of  anatomy,  neurology,  and  physiology,  and 
to  a  less  extent  upon  his  training  in  chemistry,  physiolog- 
ical chemistry,  pathology,  bacteriology,  and  physics.  And 
he  must  bear  constantly  in  mind  the  practical  clinical  ap- 
plication and  action  of  the  great  majority  of  the  drugs 
with  which  he  will  experiment. 


EXPERIMENTAL  PHARMACOLOGY 

PART  I. 


PRELIMINARY  EXERCISE. 
Assignment  of  Tables  and  Permanent  Apparatus. 

At  a  time  previous  to  the  first  laboratory  meeting  if  pos- 
sible the  students  will  arrange  themselves  according  to 
instructions  into  groups  of  four  or  five  each.  It  is  gener- 
ally desirable  (especially  if  the  students  are  unknoAvn  to 
the  instructor)  for  the  students  to  arrange  these  groups 
themselves.  This  should  usually  be  done  with  due  con- 
sideration of  the  relative  degree  of  progress  and  of 
abilit};^  which  each  student  possesses,  students  of  approxi- 
mately equal  standing  being  grouped  together. 

This  is  a  matter  of  considerable  importance  to  the 
student,  for  no  one  cares  to  drag  a  poor  student  through 
several  weeks  of  difficult  experimentation,  Avhile  on  the 
other  hand  the  poorer  students  should  not  be  cheated  out 
of  their  opportunities  to  learn  because  other  more  compe- 
tent students  do  all  of  the  work.  The  average  of  the  grades 
which  the  students  have  received  in  previous  courses  is 
usually  a  fair  basis  for  forming  these  groups. 

For  mammalian  experiments  students  work  in  the  groups 
of  four  or  five  (rarely  three  or  six  under  special  condi- 
tions). Each  group  of  four  (or  five)  is  subdivided  into 
sub-groups  of  two  (or  two  and  three)  for  work  on  frogs, 
turtles,  etc. 

Each  group  of  students  will  be  assigned  to  a  table  (or 
locker)  in  which  the  permanent  apparatus  of  the  group  is 
already  placed  and  is  in  perfect  working  condition.     This 


34  EXPERIMENTAL   PHARMACOLOGY 

apparatus  should  he  checked  up  quickly,  and  all  omissions 
or  imperfections  should  he  reported  to  the  technician  for 
correction.  A  tj^pewritten  list  of  the  apparatus  will  be  given 
to  each  group.  Each  piece  of  permanent  apparatus  be- 
longing to  a  given  table  is  marked  plainly  with  the  num- 
ber belonging  to  that  table  to  prevent  loss.  The  perma- 
nent list  includes : 

2  Simple  keys   (Fig.  135) 

2  Heart  levers   (Fig.  62) 

2  Stimulating  electrodes  (Fig.  1) 

2  Sewing  needles 

2  Signal  magnets  (Figs.  3,  4,  and  5) 

2  Induction  coils   (or  1  induction  coil  with  a  double  pole,  double  throw  knife,. 

switch,  Fig.  1) 
1  Manometer  with  signal  magnet  base  line  marker  and  tubing   (Fig.  6) 
1  Ether  bottle,  tubing  and  Hoffmann  screw  clamp  or  1  anesthetic  device  with 

oxygen  tank,  burette,  pinch  clamps  and  tubing   (Fig.  8) 

3  (or  4)   Tracheal  cannulas   (Figs.  9,  10,  and  11) 
8  Mohr's  pinch  clamps  (Fig.  12) 

3  Eecording  tambours  with  T-tubes  and  tubing   (Figs.  13  and  14) 
1  StethOgraph  drum  (Fig.  15) 

1  (or  2)   Oncometers,  T-tubes  and  tubing   (kidney,  s]Dleen,  or  intestinal  loop^ 

see  Figs.  16  and  17) 

2  Frog  boards'  (Fig.  46) 

2   (to  4)   Burettes,  tubing  and  one  funnel    (small) 

1  Large  double  clamp  (to  hold  frog  board,  etc.) 

4  (or  5)  Large  stands   (Fig.  94) 

2  Small  stands 

1  Pressure  bottle,  tube,  rope  and  pulley  (Fig.  6) 

1  Dozen  frog  clips    (Fig.  46) 

1  Ball  small  twine 

1  Ball  heavy  twine 

1  Pad   of   absorbent   cotton    (a   3-iuch  section   cut   from   a   1  lb.   roll   with   a 

large  sharp  knife) 

2  (or  3)  Arterial  cannulas   (see  Fig.  18).     More  may  be  needed 
2  Beakers,  25  and  50  cubic  centimeters   (Fig.  19) 

2  Small  flasks 

1  Tube   for  respiration  faucet    (for  artificial   respiration) 

1  Dog  board  with  mouth  rod  (Fig.  20) 

1  Thermometer 

1  Heart  oncometer    (cardiometer)    (Fig.  108) 

1  Small  white  evaporating  dish   (Fig.  22) 

1  Bladder  cannula   (Fig.  23) 

1  Sj)ool  white  thread    (heavy) 

2  Medicine  droppers   (Fig.  64) 

1  Injecting  pipette  for  frogs   (Fig.  127) 

1  Graduated  cylinder,  50  cubic  centimeters  (Fig.  24) 

1  Porcelain  dipper  (casserole)    (Fig.  25) 


LIST    OF   APPARATUS  OO 

8  Pieces  insulated  connecting  wire  (No.  18) 

2  Kymographs  (Harvard)  with  4  fans  each  (or  long  paper  kymographs,  Figs. 

26  and  27) 
2  Turtle  boards   (Fig.  28) 
1  Specimen  jar   (Fig.  29) 
6  Double  clamps  (Fig.  30) 
4  Burette  clamps   (Fig.  30) 

1  Battery  jar,  4-inch   (Fig.  31) 
6  Test  tubes 

2  Small   tables,   3    inches   and   4   inches   in   height    (to    support   kymographs, 

Fig.  32) 
1  Test  tube  brush 
1  Pound  of  ether 

Each  student  will  sign  the  foUomng  statement  at  the 
bottom  of  the  typewritten  list:  ''We,  the  undersigned, 
have  received  the  above  apparatus  in  good  condition,  ex- 
cept as  noted,  and  for  which  we  each  stand  responsible  to 
the  department. 

Date 

Signed  1 4 

2 5 

3 6 " 


Fig.  1. — Harvard  inductorium  with  dry  cell  and  simple  key  in  series.  In  the  sec- 
ondary circuit  is  a  double  pole  double  throw  knife  switch  to  which  are  connected  two 
platinum  electrodes.  By  use  of  this  combination  two  groups  of  students  can  use  one 
inductorium  and  dry  cell  without  either  group  disturbing  the  apparatus  of  the  other 
group. 


36 


EXPERIMENTAL   PHARMACOLOGY 


<:        ■■niMiiii- 


Fig.  2. — Du  Bois  Reymond  induction  coil. 


Fig.    3. — Harvard    signal    magnet. 


Fig.    4. — Signal   magnet. 


<z 


^Minufe  record 


■Seconds 


Fig.    5. — Hale's    signal    magnet.      When    this  signal    magnet    is    used    with    a    Harvard 

time    clock   possessing   a    special    adjustment    for  ten    second    and    minute    intervals,    three 

time    records    may    be    recorded    simultaneously.  (W.    Hale:    Jour,    of    Phar.    and    Fxper. 
Ther.,   1916,  viii,   p.    445.) 


MEKCURY   MANOMETER 


37 


Fig.  6. — Mercury  manometer  and  signal  magnet.  The  arrangement  of  the  tubing 
(M)  connecting  the  pressure  bottle  (R)  and  the  arterial  cannula  (and  washout,  P,  U. 
V,  W)  to  the  manometer  is  also  shown.  The  pressure  bottle  should  be  (adjustably) 
suspended  about  four  or  live  feet  above  the  taole  by  means  of  a  small  rope  {T)  passing 
through  a  pulley  {S)  on  the  ceiling.  A.  pointer  of  signal  magnet  B,  which  can  be 
made  of  a  Harvard  signal  magnet.  The  rod  of  the  signal  magnet  has  been  cut  off  and 
bent  to  pass  down  (adjustably)  into  the  hole  bored  in  the  upper  end  of  the  manometer 
board  {H)  at  K.  C,  writing  point  of  D,  the  aluminum  wire  (No.  18)  attached  to  the 
m.anometer  plunger  E,  to  the  lower  end  of  which  the  float  F,  is  attached.  The  inner 
diameter  of  the  glass  tube  N,  should  be  slightly  greater  than  one-fourth  inch  and  the  float 
is  made  (one  inch  long)  from  a  one-fourth  inch  polished  hard  rubber  rod.  The  lower 
end  of  the  float  is  bored  out  with  a  3/16  inch  drill  to  float  (full  of  air)  on  the  surface 
of  the  mercury  G.  Polished  drill  rod  steel  (1/32  inch  in  diameter)  is  used  for  the 
plunger  which  is  driven  into  a  small  drill  hole  in  the  upper  part  of  the  float.  I,  sup- 
porting rod  of  the  manometer.  J,  glass  T-tube  connected  by  rubber  tubing  (F)  to  the 
right  limb  of  the  U-tube.  L,  adjustable  brass  (or  iron)  wire  (Is  inch)  from  which  a 
thread  (Z)  supports  a  small  weight  to  hold  the  writing  point  on  the  drum.  O,  O, 
wires  running  to  the  signal  magnet  base  line  marker  {B)  from  X,  X,  binding  posts 
which  receive  electric  impulses  from  the  time  clock.  It  is  better  but  more  difficult  and 
expensive  for  the  U-tube  to  have  a  side  outlet  blown  on  the  right  hand  limb  in  place 
of  the  T-tube  here  shown.  The  left  hand  limb  of  the  U-tube  should  be  twelve  inches 
long.  A  little  oil  is  placed  around  the  float.  The  U-tube  and  T-tube  are  attached  to 
the   board   by    copper   wires   passed  through    holes   and   twisted    together  behind   the   board. 


EXPERIMENTAL   PHAEMACOLOGY 


Special  apparatus  for  individual  experiments  will  be 
given  out  from  time  to  time  as  needed. 

Drum  paper  will  be  furnished,  10  sheets  at  a  time,  as  re- 
quired. 


Fig.  7. — Harvard  shielded  electrodes. 


Ether  will  be  given  out  in  1  lb.  cans  on  presentation  of  a 
signed  order  blank.  Ether  used  beyond  the  amount  esti- 
mated to  be  necessary  will  be  charged  for  at  cost. 


Fig.  8. — Ether  bottle   (3-necked  Woulff,  SOO  c.c.)   with  regulating  clamp.     The  short  T-tubes 
are  made   of   one-half   inch   brass   tubing    (see   chapter   on   shop    work). 

Drugs  and  experimental  material  will  be  furnished  by  the 
department  as  needed.  The  cost  of  wasted  material  will 
be  deducted  from  the  student 's  breakage  deposit. 


TRACHEAL    CANNULAS 


39 


Fig.    9. — lyarge    (one-half    inch)     size    tracheal    cannula. 


Fig.    10. — Medium    (three-eighths   inch)    size    tracheal   cannula. 


Fig.    11. — Small    (one-fourth   inch)    size   tracheal    cannula. 


40 


EXPERIMENTAL   PHARMACOLOGY 


Wi" 


Fig.   12. — Mohr  pinch  cocks. 


Fig.    13. — Marey  tambour. 


Swall  5izea  cup 

I  for 
6upporHn^  rod 


Tube  io 
Oncometer 


tamdaur  cup 


Medium  sized  cup. 


4r»'      frj  f?<rrd  l  openings  for 
'  ''  \supporrin^  rod 


1     y 


Lar(je  sized  cup 


Fig.    14.— Adjustable    tambour   with  three   interchangeable   bowls.      All   parts   approximately 

half  natural  size. 
It  is  exceedingly  important  for  the  student  to  have  some  large-bowled  tambours. 
None  of  these  are  at  present  on  the  market  and  each  laboratory  must  provide  for 
itself  The  ordinary  Marey  tambour  is  wholly  inadequate  for  many  forms  _  of  work 
because  the  bowl  is  entirely  too  small.  The  adjustable  form  here  shown  ^^ Ji^ghly 
recommended  for  all  purposes  for  which  tambours  can  be  used.  A  mechanical  drawing 
of  this  tambour  is  shown  in  the  chapter  on  shop  work  where  a  cheap  form  ot  large- 
bowled  tambour  is  also  described. 


STETHOGRAPH    DRUM,    KIDNEY    OXOOMETER 


41 


Fig.  15. — Stethograph  drum,  made  of  2J4  inch  brass  tubing.  The  drum  has  a  length 
of  1  ^  inches  and  wire  rings  are  soldered  around  the  edges  to  act  as  flanges  for  holding 
on  the  strings  used  to  tie  down  the  rubber  membranes.  (For  the  method  of  tying  on 
these  membranes  and  attaching  the  screws  in  the  center,  see  Fig.  374  in  the  chapter  on 
shop  work.)  These  stethograph  drums  are  not  on  the  market  but  can  easily  be  made 
by   any  janitor   or  technician. 


Fig.  16. — Kidney  oncometer,  about  2/3  natural  size,  made  of  sheet  brass.  The  lid 
is  placed  under  the  kidney  and  the  box  closes  over  the  organ.  The  latches  are  turned 
inward.  The  opening  out  of  the  oncometer  is  at  the  rear  as  seen  in  the  picture  and  the 
opening  passes  forward  in  the  square  tube  into  which  the  round  connecting  tube  is 
soldered. 


42 


EXPERIMENTAL   PHARMACOLOGY 


tube  to  recorder 


enclosed 
membrane 


Fig.    17. — Roy's   kidney   oncometer. 


iflliinitfliiiliitniti 
iilliMiiniliilllilil/iiiiUMiri,,, 


Fig.  18. — Arterial  cannula,  used  also  for  injecting  into  veins.  This  is  by  far  the 
best  cannula  for  recording  blood-pressure  or  injecting  from  a  burette.  Such  cannulas 
are  made  to  order  by  glass-blowing  firms  (see  page  515).  The  opening  in  the  point 
should  be  about  1/32,  3/64  or  1/16  inch  in  diameter  for  most  purposes.  The  usual 
difficulty  is  to  get  the  smaller  sizes. 


LABORATORY  APPARATUS 


43 


Fig.    19. — Beaker. 


Fig.    20. — Dog   board   and    mouth    rod.      Made    of    a   pine   board    1    foot   wide    and   4J4 
(or  5)    feet  long.     Not   on  the  market. 


Fig.    21. — Animal   board   and   head   holder    (for   rabbits    or   cats). 


Fig.    22. — Small,   white    evaporating   dish. 


44 


EXPEKIMENTAL   PHARMACOLOGY 


^^^^^$>:^:^^:^^$^^^^^^^>^?::^^ 


Fig.    23. — Glass    bladder    cannula,    nearly    natural    size. 


Fig.    24. — Graduated   cylinder. 


Fig.    25. — Casserole. 


LONG   PAPER    KYMOGRAPHS 


45 


Fig.   26. — Harvard   long  paper  kymograph. 


Fig.    27. — Hiirthle   long  paper   kymograph. 


46 


EXPERIMENTAL    PHARMACOLOGY 


Fig.  28. — Turtle  board,  made  of  cheap,  scrap,  pine  lumber  (old  goods  boxes).  A 
hooked  wire  (sharpened)  is  attached  to  the  front  end.  The  hook  catches  in  the  lower 
jaw    ("chin")    of  the  turtle.     The  feet  are  tied  out  tightly  to   the   staples. 


Fig.    29. — Specimen  jar. 


Fig.    30. — Upper   picture,   burette   clamp;   lower  picture,   double   clamp    (Harvard). 


BATTERY  JAR^   SMALL  TABLES 


47 


Fig.     31. — Battery    jar    (4x5    inches). 


Fig.    32. — Small  wood   tables   for  supporting  apparatus,   Harvard   kymographs,   etc. 


48 


EXPERIMENTAL   PHARMACOLOGY 


Each  student  should  provide  himself  with  a  dissecting- 
gown,  a  cheap  note  book  for  rough  notes,  and  the  follow- 
ing dissecting  instruments : 

1    (or  2)   Serrefins   (bull-dog  artery  clamps)    (Fig.  33) 

1   (or  2)   Hemostats  (Fig.  34) 

1  Pair  small  sharp-pointed  straight  forceps  (Fig.  35) 


Fig.    33. — Serrefine. 


Fig.   34. — Hemostat. 


r^i^li-VMW.i'^/'Mlllnuat 


Fig.    35. — Small    sharp-pointed    dissecting    forceps. 


In  addition  to  this,  eacli  group  of  students  should  further 
provide  itself  with  the  following  instruments  for  use  of  the 
group  as  a  whole : 

2  Good  dissecting  scalpels.  (There  is  only  a  very  limited  use  for  the  knife, 
hence  not  more  than  two  need  be  provided.  This  may  prevent  many 
poor  dissections  and  bad  hemorrhages)    (Fig.  36) 

2  Aneurism  needles   (Figs.  37  and  38) 

2  Pairs  of  large  blunt-pointed  dissecting  forceps   (Fig.  39) 

1  Pair  of  smaller  blunt-pointed  dissecting  forceps  (Fig.  40) 

3  Pairs  of  dissecting  scissors,  one  large,  two  small   (Fig.  41) 

2  Dissecting  probes  (Fig.  42) 

1  Large  moderately  sharp-pointed  dissecting  forceps  to  be  used  for  inserting 
cannulas  (Fig.  43) 


DISSECTING  INSTRUMEJSTTS 


49 


Fig.    36. — Scalpel 


^-i -'~ .  -^  ^^-t-J^'^V^^'.k^S-k.i^ki.Kkt.^^^.J^^^k^^^kl-iJJk^.^'lto,^^^ 


Fig,    37. — Small    aneurism    needle. 


Fig.    38. — Large    aneurism    needle. 


dmnm 


(^uvv^^.^.^.^.^.w^v.^^^^-^^^v-^^^^^^-.-.^^v■^^\\\v■v\^^.^.^v^^\' 


Fig.    39. — lyarge   blunt-pointed   dissecting  forceps. 


^^^^^^SS^^N^^^^W? 


i"r'7#") 


Fig.    40. — Small    blunt-pointed    dissecting    forceps. 


Fig.    41. — Dissecting   scissors. 


Fig.    42. — Dissecting   probe    (dental). 


50 


EXPERIMENTAL   PHARMACOLOGY 


Students  are  warned  not  to  buy  the  so-called  "sets"  of 
dissecting  instruments.  Also  do  not  buy  a  lot  of  unneces- 
sary instruments.  Students  who  have  had  human  dissec- 
tion will  usually  already  possess  most  of  the  necessary 
(and  a  good  many  unnecessary)  instruments. 

Each  student  must  be  provided  with  a  permanent  note 
book  in  which  is  written  up  a  careful  description  of  each 
experiment  performed.  This  note  book  should  be  well 
bound,  its  dimensions  should  be  about  7%  inches  b}^  10^/4 
inches,  and  it  should  contain  about  150  pages.  The  paper 
should  be  of  good  quality  and  all  permanent  notes  must 


Fig.    43. — L,arge    moderately    blunt-pointed    dissecting    forceps. 


Fig.    44. — Needle    holder. 


be  written  in  ink.  Avoid  typewritten  or  loose  leaf  note 
books.  Either  the  original  or  blue  print  copies  of  all  typ- 
ical tracings  obtained  should  be  pasted  in  the  permanent 
note  book  and  fully  explained  in  the  notes.  It  is  urged  that 
notes  be  made  brief,  but  strictly  to  the  point.  It  requires 
only  a  few  paragraphs  for  a  student  who  fully  understands 
an  experiment  to  tell  what  he  did,  how  he  did  it,  and 
what  his  results  show.  A  student  should  not  hesitate  to 
admit  that  any  given  experiment  was  a  failure,  or  that 
part  of  his  results  or  tracings  are  wrong.  Such  errors  are 
frequent  and  will  be  understood  at  once  by  the  instructor, 
and  it  is  exceedingly  valuable  to  the  student  to  be  able  to 


LABORATORY  DIRECTIONS  51 

recognize  his  own  failures  and  if  possible  to  determine  the 
cause  of  the  failure.  And  it  is  of  even  greater  importance 
to  the  student  to  be  able  to  recognize  and  to  show  what  re- 
sults he  should  have  obtained  in  an  experiment  which  has 
apparently  failed.  Not  only  the  student,  but  especially 
the  instructor,  should  constantly  be  on  the  watch  for  atyp- 
ical or  unexpected  results.  Such  chance  observations  have 
often  furnished  the  basis  for  valuable  discoveries. 

Blue  print  copies  of  the  best  original  tracings  {chosen  hy 
the  instructor)  should  be  made  in  the  department,  usually 
by  the  technician,  and  should  be  furnished  to  the  student  at 
a  price  which  is  just  sufficient  to  cover  the  cost  of  the  blue 
print  paper.  (For  directions  for  making  blue  prints,  see 
chapter  on  photography,  page  510.) 

It  is  important  that  the  permanent  notes  for  each  ex- 
periment be  written  up  as  soon  as  possible  after  the  ex- 
periment is  performed.  The  records  or  tracings  should  be 
labeled  in  full  and  great  care  should  be  used  to  make  them 
as  neat  and  accurate  as  possible.  No  more  drum  space 
than  is  absolutely  necessary  should  be  used  in  making  each 
tracing.  The  drum  paper  should  always  be  smoked  good 
and  Mack.  This  is  important  for  blue  printing  and  for 
publication  if  the  instructor  or  anyone  else  should  care  to 
have  any  tracing  reproduced.  It  is  also  necessary  for  mak- 
ing lantern  slides.  (See  chapter  on  photography,  page 
500.) 

Each  group  of  students  will  be  assigned  to  a  table  on 
which  to  work.  If  a  sufficient  nimiber  of  tables  and  the 
floor  space  are  available,  it  is  advisable  for  each  group  to 
have  two  tables,  one  for  the  experiment  and  the  other  to  be 
used  as  a  side  table  for  arranging  apparatus,  etc.  ^'\'Tien 
frogs  or  turtles  are  used  then  the  two  sub-groups  (of  two 
or  three)  may  each  have  a  table.  If  only  one  table  is  avail- 
able, then  for  frog  or  turtle  work  the  two  sub-groups  should 
w^ork  one  at  each  end  of  the  table.  It  is  preferable  that  the 
drawers  or  lockers  for  the  permanent  apparatus  be  secured 


52 


EXPERIMENTAL   PHARMACOLOGY 


by  padlocks  and  that  the  students  themselves  furnish  their 
OA\ai  locks.  This  relieves  the  instructor  of  much  unneces- 
sary annoyance. 

Special  arrangements  will  be  made  for  individual  experi- 
ments or  for  those  requiring  apparatus  which  can  not  be 


Fig.  45. — Large  bottle  for  holding  stock  salt  solution.  Normal  tap  water  saline 
(6   Or   7   grams   of   NaCl   to   the  liter)    is   suitable   for  most   forms   of  frog  or   turtle   work. 

Locke's  solution  contains:— NaCl,  0.92%;  KCl,  0.042%;  CaCU,  0.024%  (crystals); 
NaHCOs,  0.015%;  Dextrose,  0.1%.  Ringer's  solution  contains:— NaCl,  0.6%;  KCl, 
0.0075%;  CaCU,  0.01%  (dried);  NaHCOa,  0.1%.  Tyrode's  solution  contains: — NaCl, 
0.8%;  KCl,  0.02%;  CaCla,  0.02%  (crystals);  NaHCOs,  0.1%;  MgCls,  0.01%;  NasHPOi, 
0.005%;  glucose,  0.1%.     Dissolve  the  NaHCOs  before  adding  the  CaCl2  in  each  case. 

distributed  to  the  class.  Much  variation  will  be  found  in 
this  respect  in  various  schools.  Many  pieces  of  apparatus 
must  be  made  up  to  fit  the  experiment  or  the  facilities  of  the 
laboratory.    (See  chapter  on  shop  work,  page  470.) 


ETHER   ANESTHESIA  06 

A  salt  solution  (Locke,  Ringer,  Tyrode,  etc.)  will  be 
placed  in  a  large  supply  bottle  in  the  laboratory.  (Fig.  45.) 
Sodinm  citrate  solution  for  blood  pressure  work  will  be 
supplied  by  the  technician  as  needed.  Unnecessary  ivastage 
ivill  he  charged  at  cost. 

Specific  detailed  directions  are  given  in  the  text  for  the 
performance  of  each  experiment,  but  both  students  and 
instructors  should  be  constantly  on  the  watch  for  oppor- 
tunities to  improve  the  methods  and  technic  given  or  to 
introduce  new  and  better  experiments.  The  writer  believes 
this  to  be  the  best  test  of  the  vitality,  spirit,  and  progress 
of  any  course  and  he  never  teaches  the  same  set  of  experi- 
ments tmce,  but,  on  the  contrary,  he  is  constantly  trying 
to  improve  or  drop  the  old  experiments  and  to  add  newer 
and  better  ones.  This  is  even  more  true  for  apparatus,  and 
the  writer  sincerely  hopes  that  all  students  and  teachers 
into  whose  hands  this  book  may  come  will  gladly  contribute 
all  that  they  can  toward  devising  better,  simpler,  and 
cheaper  apj)aratus. 

More  experiments  are  given  in  this  book  than  the  class 
will  probably  be  able  to  perform.  The  instructor  will  se- 
lect those  best  suited  for  the  class  and  for  the  facilities  of 
the  labor atory.  Experiments  entirely  different  from  those 
in  the  text  may  be  substituted  at  any  time. 

Not  more  than  fifteen  minutes  should  be  occupied  in 
checking  apparatus.  Immediately  thereafter  proceed  as 
follows : 

EXPERIMENT  I. 

Ether.     (Action  on  the  Central  Nervous  System. — Cere- 
brum.) 

1.  Under  an  inverted  battery  jar  (Fig.  31)  place  a  full 
grown  normal  frog.  Take  a  small  piece  of  absorbent  cot- 
ton and  pour  a  few  cubic  centimeters  of  ether  on  it.  Raise 
the  edge  of  the  battery  jar  a  little  and  slip  the  cotton  under 


54 


EXPEEIMElvrTAL   PHARMACOLOGY 


the  jar.  The  ether  vapor  will  fill  the  jar  and  the  frog  will 
presently  begin  to  show  symptoms  from  the  action  of  the 
drug.  Watch  the  animal  closely.  Are  there  pupillary, 
changes?  Can  you  distinguish  such  stages  as  that  of  im- 
perfect consciousness,  excitement,  and  anesthesia  in  the 
symptoms  exhibited  by  the  frog!  Touch  the  animal  from 
time  to  time  and  when  all  the  reflexes  have  disappeared, 
remove  it  from  the  jar  and  quickly  fasten  it  down  to  a 
frog  board  (Fig.  46)  with  clips,  in  the  position  shown  in 
Fig.  47.  Do  not  injure  the  animal  hy  unnecessary  pres- 
sure. Place  a  small  piece  of  cotton  over  the  frog's  nose 
and  mouth  and  pour  a  few  drops  of  ether  on  the  cotton. 


Fig.   46. — Frog  board  and  clip   (Harvard).      (See  chapter  on  shop  work.) 

With  small  scissors  quickly  make  a  median  longitudinal 
incision  in  the  skin  above  the  brain.  With  the  sharp  point 
of  a  scalpel,  held  in  the  same  manner  as  one  holds  a  pen 
in  writing,  make  a  series  of  short  shallow  cuts  in  the  skull 
directly  in  the  median  line  over  the  cerebrum  (Figs.  47  and 
48).  When  an  opening  has  been  made  through  the  skull, 
the  sharp  point  of  a  small  pair  of  scissors  may  be  care- 
fully inserted  and  the  opening  thus  cut  larger.  Be  careful 
not  to  injure  the  brain.  Check  hemorrhages  with  small 
plugs  of  cotton.  Expose  both  lobes  of  the  cerebrum  and 
then  with  the  point  of  the  scalpel  carefully  remove  from 
behind  forwards  the  entire  cerebrum.  Check  hemorrhages 
with  cotton  plugs  for  a  while,  but  do  not  compress  the  optic 


Cvfdneou5  branch  of  femorsldrt. 

M.  6/ufaeus 
M.  Rectus  interior 
M.  V^isfus  exfernus 
Sciafic  'arfery____A 
M.  Triceps  femoris     ^^ 
M.  Biceps 
Art  Peroncci 

Art.  Surd/ is 
Art  cut  (jenu  /H  inf. 

M.  Peroneus 
n.  Jib  I  alls  anficus 
Art.  waiieoldris  lateralis 
Art  ma/leo/dris  medid/ij 
Art  Tardea. 


fl.  Adductor  ma^nu^ 

N.  Tibialis 
* 

A'.  Peroneus 
'r  N.  3uralij 
///)  N.Cut  cruris  M 


-^  Branch  of  Tibial 
nerve  to  Oastroc- 
nemius  muscle 


Fig.  47. — Dissection  of  a  frog  showing  position  of  the  brain,  sciatic  nerve  and  arteries  and  muscles 

of   the   hind   limb. 


ACTION    OF    CHLOROFORM 


55 


lobes.  Remove  the  cotton  plugs  and  sew  the  skin  together 
over  the  skull  with  a  needle  and  thread,  tie  a  thread  (not 
tightly)  around  the  left  hind  foot  and  place  the  animal  on 
moist  cotton  in  a  casserole  (Fig.  25)  to  recover. 

The  action  of  ether  is  largely  manifested  on  the  cerebrum, 
especially  in  higher  animals.    When  the  animal  recovers, 


—  0/ factory  nerve 
-Olfactory  lobe 


Cerebrum 

.Pineal  body 
Jhahmencephdilon 

-  Optic  lobe 

--Cerebellum 
--Fourth  ventricle 
-Medulla  oblongata 
Long,  fissure  of  ^9^^  vent 


Fig.    48. — Frog's    brain. 

carefully  compare  its  spontaneous  and  reflex  actions  Avith 
those  of  a  frog  which  is  just  being  anesthetized  and  also 
with  the  condition  of  the  frog  after  the  anesthesia  is  com- 
plete. 

Chloroform.     (Action  on  the  Central  Nervous  System. — 
^  Optic  Lobes.) 

2.  In  the  same  manner  as  in  the  above  experiment,  anes- 
thetize a  frog  with  a  feiv  drops  of  chloroform.    Expose  the 


56 


EXPERIMENTAL   PHARMACOLOGY 


rigJit  optic  lobe  and  remove  it.  Be  careful  to  avoid  injuring- 
the  thalamencephalon  or  cerebellum.  Do  not  use  too  much 
chloroform.  It  Avill  produce  a  profound  anesthesia  and  the 
animal  may  not  survive.  Tie  a  thread  (not  tightly)  around 
the  rigJit  fore  leg  and  place  the  frog  on  moist  cotton  in  a 
covered  battery  jar  to  recover.    A  fcAV  hours  later  (or  next 


Position  of 

foramen 

magnum 


in,or  sharp 
pointed  probe 


Fig.    49. — Method   of   pithing   a   frog.      A  towel   is    sometimes    wrapped    around    the   animal 

to   facilitate   holding  it. 

day)  carefully  observe  the  actions  of  the  animal  and  com- 
pare these  Avith  those  of  the  frog  mth  the  cerebrum  re- 
moved. How  do  these  symx)toms  differ  from  those  exhib- 
ited by  a  frog  which  is  just  being  anesthetized?  Theoret- 
ically Avhat  symptoms  should  be  shoAvn  by  a  frog  which  was 
injected  with  a  drug  that  Avould  depress  the  cerebrum  alone! 
Or  the  optic  lobes  alone!  Place  both  frogs  in  the  water  and 
observe  their  movements.  It  will  be  instructive  if  another 
frog  can  be  operated  on  and  the  left  optic  lobe  removed. 


ETHER;  ETHYL   CHLORIDE 


57 


What  relation  do  the  optic  lobes  of  the  frog  bear  to  the  cere- 
bellum of  mammals? 

3.  Learn  the  technic  of  pithing  a  frog  if  yon  have  not  al- 
ready done  so.    (See  Fig.  49.) 

Ether,  Ethyl  Chloride,  Chloroform,  Ethyl  Bromide. 
(Irritability  and  Conductivity  of  Nerve.) 

4.  (a)  After  pithing  place  a  frog  face  downward  on  the 
frog  board  and  dissect  out  the  sciatic  nerve  from  its  origin 


i-7b   muscle  lever ^ 
To 'Secondary  coil 

Fig.    50. — Harvard   moist   chamber. 

at  the  spinal  cord  down  to  the  knee.  Avoid  injuring  the 
nerve.  Tie  a  thread  to  the  nerve  and  then  dissect  the  gas- 
trocnemius muscle  (Figs.  47  and  60)  loose  from  the  bones 
of  the  leg.    Cut  the  tendo  Achillis  long  and  then  divide  the 


58 


EXPERIMENTAL   PHARMACOLOGY 


femur  and  thigh  muscles,  but  leave  the  sciatic  nerve  intact 
and  attached  to  the  gastrocnemius  muscle.  Cut  the  tibia 
and  fibula  just  below  the  knee  and  free  the  gastrocnemius 
from  the  remaining  tissues  of  the  leg. 


Fig.   51. — Harvard  muscle   lever. 


The  cut  end  of  the  femur  should  now  be  fastened  in  the 
clamp  of  a  moist  chamber  (Fig.  50)  and  a  pin  hook  is  passed 
through   the   tendo   Achillis   as   illustrated.     The   thread 


Fig.    52. — Harvard   gas   chamber. 


passes  down  to  a  muscle  lever  (Fig.  51)  which  writes  on 
a  smoked  drum.  A  gas  chamber  (Fig.  52)  held  in  a  burette 
clamp  (Fig.  30)  is  placed  in  position  near  the  muscle  (to  the 


ETHER,  ETHYL   CHLORIDE 


59 


right  in  the  illustration),  and  by  help  of  the  thread  the 
sciatic  nerve  is  drawn  through  the  holes  in  the  gas  chamber 
and  across  the  two  needle  electrodes  which  are  connected  to 
an  induction  coil  arranged  for  single  shocks.  (See  Fig.  1.) 
By  means  of  a  rubber  tube,  one  of  the  side  tubes  of  an  ether 
bottle  is  now  connected  with  one  of  the  tubes  leading  into 
the  gas  chamber.     The  boot  electrodes   (which  have  been 


Fig.  53. — Ether  bottles  showing  method  of  administering  air  and  ether  (chloroform) 
to  ati  animal  with  the  chest  open,  or  for  passing  ether  (chloroform)  vapor  through  the  gas 
chamber. 

soaked  in  salt  solution  and  now  have  been  filled  with  zinc 
sulphate  solution)  may  be  iDlaced  just  to  the  right  of  the  gas 
chamber  and  the  end  of  the  sciatic  nerve  is  laid  across  the 
tips  of  the  boots.  Keep  the  nerve  and  muscle  moist  with 
normal  salt  solution.  The  boot  electrodes  are  also  arranged 
so  that  single  shocks  may  be  sent  through  them  when  de- 


60 


EXPEKIMENTAL   PHARMACOLOGY 


sired.  The  drum  should  turn  at  a  moderate  speed.  Some 
ether  is  now  placed  in  the  ether  bottle  and  by  means  of  a 
hand  bellows  a  current  of  air  and  ether  vapor  can  be  passed 
through  the  gas  chamber  (Figs.  52  and  53).  Just  before  the 
ether  is  applied  several  contractions  of  the  muscle  should 
be  recorded  to  serve  as  normal  controls.  These  controls 
should  be  obtained  both  from  the  needle  and  from  the  boot 


Fig.    54. — Three   forms    of    containers    for   ethyl    chloride.      The    Gebauer    container   is 

preferred. 


electrodes.  These  records  should  be  carefully  preserved 
and  compared  with  those  obtained  later.  When  the  normals 
have  been  secured  then  pass  a  small  amount  of  ether  vapor 
through  the  chamber  and  then  again  stimulate  the  nerve 
with  the  needle  electrodes.  What  action  has  the  ether  had 
on  the  irritability  of  the  nerve?  Stimulate  with  the  boot 
electrodes.  Has  the  conductivity  of  the  nerve  been  af- 
fected!   Is  this  a  fair  test? 


ETHYL    CHLORIDE,    CHLOROFORM,    ETHYL    BROMIDE 


61 


(b)  Blow  out  the  ether  vapor  with  pure  air  and  repeat 
the  stimulations.    Does  the  nerve  return  to  normal? 

(c)  With  a  Gebauer  or  Kelene  tube  (Fig.  54)  spray  a 
little  ethyl  chloride  through  the  gas  chamber.  Do  not 
freeze  the  nerve.  Quickly  repeat  the  stimulations  and  note 
the  effects  on  the  nerve.    What  do  you  observe? 

(d)  Blow  out  the  ethyl  chloride  from  the  gas  chamber 
and  obtain  new  "normal"  contractions  of  the  muscle.    If 


ii!ill!!!l|i!llliil>?^ 


Fig.    55. — Method    of    smoking    drums    (in    a    hood).       Benzol    is    placed    in    the    one    pint 

milk   bottle. 


the  nerve  is  dead  a  new  preparation  should  be  made.  Place 
a  few  drops  of  chloroform  in  the  ether  bottle  and  blow  the 
vapor  of  this  through  the  gas  chamber.  Again  stimulate 
the  nerve  with  the  needle  and  with  the  boot  electrodes. 
What  do  you  observe?  What  can  you  say  as  to  the  relative 
action  of  ether,  ethyl  chloride,  and  chloroform  on  isolated 
nerve  trunks?  Ethyl  bromide  may  also  be  tried  similarly. 
Before  taking  down  the  apparatus  stimulate  the  muscle 
itself  directly  a  few  times  to  determine  its  condition.  This 
is  easily  done  if  a  very  fine  copper  wire  instead  of  a  thread 


62 


EXPEEIMEjSJ"TAL  phaemacology 


Veislleflfack 


Fig.  56.— Automatic  shellacing  pan  and  drying  rack  for  drum  records.  Varnish  is 
made  by  dissolving  the  best  granular  white  shellac  m  alcohol.  A  large  excess  o*  the 
shellac  should  be  present,  and  solution  is  allowed  to  go  on  for  a  week  or  more  (shake 
up  thoroughly  several  times),  at  the  end  of  which  time  the  clear  supernatant  solution 
is  decanted  and  placed  in  a  well  stoppered  bottle  to  prevent  evaporation  of  the  alcohol. 
If  this  occurs  small  particles  of  the  shellac  precipitate  out  and  may  spoil  the  varnislied 
records  by  being  deposited  as  white  specks  all  over  the  black  surface  of  the  tracing. 
Orange  shellac  is  somewhat  more  soluble  than  the  white  but  not  so  satisfactory  because 
of  the  yellowish  color  it  gives  to  the  records.  This  is  very  undesirable  if  any  records 
are  to  be  blue-printed,  photographed  or  used  for  publication.  Cheap  varnishes  made 
of  gasoline  and  rosin,  etc.,  are  sometimes  used.  A  high  grade  brass  lacquer  (such  as 
Kahlbatim's  metallfurniss,  farblos)  may  often  be  much  diluted  with  alcohol  and  thus 
made  into  an  excellent  varnish  for  records. 


VAENISHING    AND    TRIMMING    RECORDS 


63 


Fig.  57. — \^arnishing  pan  (12  inches  long,  7  inches  wide),  used  for  varnishing 
records  from  long  paper  kymographs.  The  record  is  cut  apart  on  the  drum,  one 
person  holding  each  end.  The  smoked  surface  is  turned  upward.  One  person  steps  on 
a  stool  (or  short  stepladder)  and  lifts  one  end  of  the  record  high  in  the  air.  The 
assistant  dips  the  other  end  of  the  record  into  the  varnish  and  lifts  up  his  end  of  the 
record  as  the  other  end  of  the  tracing  is  lowered.  The  tracing  is  suspended  from  each 
end  like  a  hamrnock  on  the  rack  (shown  in  Fig.   56)  to  dry. 


Fig.    58. — Print   and  tracing   trimmer. 


64 


EXPERIMENTAL   PHARMACOLOGy 


is  used  to  connect  the  pin  hook  in  the  tendo  Achillis  to  the 
muscle  lever.  The  secondary  terminals  can  then  be  at- 
tached to  the  muscle  lever  and  to  the  muscle  clamp. 

Ethyl  Chloride.     (Local  Anesthesia.) 

5.  Hold  a  Gebauer  or  Kelene  tube  about  10  or  12  inches 
from  the  hand  and  open  the  valve  a  little.  A  small  spray 
of  the  drug  mil  be  forced  out.    Why?     Direct  this  spray 


-Time 
circuit 


r^ •— i — — - 

Tieceptacle  for 
electrodes  when  not  in  use. 


'Sprincj  key 


The  wire  of  ihe  electrodes  Should  be  6 

ft  lonq  ana 

lamp-cord 


made  of  yery  small  sized 


Fig.  59. — Convenient  method  of  arranging  the  inductorium,  battery,  key  and  elec- 
trodes to  avoid  tearing  down  the  apparatus  at  each  period.  The  inductorium  is  out  of 
the  way  and  always  ready  for  use. 

against  the  back  of  the  hand.  A  white  frost  will  soon  ap- 
pear on  the  skin  and  hairs.  A  few  seconds  after  this  frost 
begins  to  form  stop  the  spray  and  quickly  examine  the  sen- 
sibility of  the  skin  in  the  area  affected.  To  what  is  this 
action  due?  To  A¥hat  clinical  use  might  this  be  applied! 
Can  you  think  of  other  substances  having  a  similar  ac- 
tion? Is  this  action  of  ethyl  chloride  in  any  way  similar 
to  that  of  ether,  ethyl  chloride,  or  chloroform,  on  the  irrita- 
bility or  conductivity  of  nerve  trunks  ?  What  is  the  boiling- 
point  of  ethyl  chloride  ?  If  a  local  anesthetic  be  applied  to  a 
mixed  nerve  trunk  will  all  the  constituent  fibers  be  equally 
affected  at  the  same  time? 


Fig.  60. — Dissection  of  a  frog  to  show  the  position  of  the  heart,  vagus  nerve  and  the  muscles 
of  the  hind  limb.  The  electrodes  are  in  position  for  stimulating  the  vago-sympathetic  trunk.  It 
is  often  desirable  to  fasten  the  electrodes  in  this  position  (in  a  burette  clamp)  so  that  the  animal 
may  not  be  disturbed  when  the  nerve  is  stimulated. 


ACTION   OF  ETHER  OjST   THE   HEART  65 

EXPERIMENT  II. 

Ether.     (Action  on  the  Heart. — Dissection  for  the  Vagus 
Nerve  in  the  Frog.) 

1.  Pith  a  frog  and  clamp  it  clown  to  the  iDoard  with  the 
"ventral  side  up,  as  slioAvn  in  Fig.  60.  With  sharp  scissors 
split  the  abdominal  and  thoracic  walls  in  the  median  line 
forward  into  the  skin  over  the  floor  of  the  mouth.  If  pos- 
sible avoid  dividing  the  abdominal  vessels.  Cut  open  the 
girdle  of  bones  directly  over  the  heart  (which  should  be 
carefully  avoided)  with  the  scissors.  Then  pull  the  tho- 
racic cavity  widely  open  by  stretching  out  the  fore  legs  from 
side  to  side.  Reset  the  clamps  holding  these  legs.  Refer 
to  Fig.  60  and  identify  the  glossopharyngeal,  hypoglossal, 
and  brachial  nerves.  Near  the  angle  of  the  jaw  dissect 
down  carefully  with  a  probe  and  fine-pointed  forceps  until 
the  lar}mgeal  branch  of  the  vagus  and  the  vago-s^nnpathetic 
nerves  come  into  sight.  For  the  method  of  union  between 
the  sympathetic  chain  and  the  main  trunk  of  the  vagus 
nerve  see  Fig.  61.  The  S3mipathetic  fibers  pass  forward 
in  the  thorax  to  the  base  of  the  skull  where  they  turn  back- 
wards and  unite  with  the  vagus  nerve  to  be  distributed 
^\ith  the  vagus  to  the  heart,  lungs,  etc.  AYlien  the  vago- 
sympathetic nerve  has  been  found  it  should  be  pulled  out- 
ivard  a  little  and  the  points  of  the  electrodes  slipped  be- 
neath the  nerve.  With  a  tetanizing  current  of  medium 
strength  stimulate  the  nerve  and  see  if  the  heart  stops. 
This  is  to  identify  the  nerve.  Do  not  stimulate  the  nerve 
'Ciny  longer  than  is  absolutely  necessary,  for  the  ]ierve  end- 
ings are  easily  fatigued  and  may  not  be  able  to  stop  the 
heart  later  after  your  apparatus  is  all  arranged. 

The  heart  is  now  freed  from  the  pericardium  and  con- 
nected with  a  heart  lever  l^y  means  of  a  pin  hook  and  a 
thread  as  shown  in  Fig.  63.  The  tip  of  the  ventricle  is  at- 
lached  to  the  pericardium  by  a  small  ligament  called  the 


66 


EXPEKIMENTAL   PHARMACOLOGY 


freniim.  Pick  this  up  with  the  forceps,  sever  it,  and  at  the 
point  where  it  is  attached  to  the  heart  stick  the  pin  hook 
(which  should  be  small)  through  the  tip  or  the  ventricle. 
Adjust  the  heart  lever  to  write  about  one-half  inch  from 
the  lower  edge  of  the  drum  and  see  to  it  that  the  tracing 


N.GI0550- 

pharyncjeai 

Ganalion  of  Vacjus 
5  ympa-thefic/cha'm 


Art   Subclavian 


Spinal       ■'  / 
nerves 


i1  Levator 

gnquli  scapulde 


Vertebral 
column 


^^^^"■^  ^."  (/Iff^r  Qdskell ) 

Descendinq         ^    ' 
Aorta      ^ 


Fig.  61. — Diagrammatic  dissection  to  show  the  origin  and  course  of  the  sympa- 
thetic chain  and  the  union  of  the  vagus  and  the  sympathetic  fibers  for  the  heart  in  the 
frog   (Gaskell). 


Fig.  62. — Heart  lever.  The  rod  is  made  of  3/16  inch  round  brass  rod  into  the  end 
of  which  a  small  hole  is  drilled.  A  small  block  of  wood  fiber  or  hard  rubber  is  attached 
to  the  rod  by  a  small  wire  nail  which  passes  (loosely)  through  the  wood  fiber  block  and 
is  then  driven  (tightly)  into  the  hole  in  the  end  of  the  rod.  The  writing  lever  is  a 
very  thin  strip  split  from  a  long  (10  or  12  indies)  section  of  a  bamboo  fishing  pole. 
This  lever,  which  is  very  light  and  limber,  passes  (tightly)  through  an  oblong  hole  in 
the  upper  part  of  the  wood  fiber  block.  A  paper  or  celluloid  (used  photographic  film) 
writing  point  is  attached  by  mucilage  or  by  a  cement  made  by  dissolving  a  photographic 
film  in  acetone.  These  levers  are  entirely  satisfactory  for  the  hearts  of  frogs,  turtles, 
for   uterine   strips,    etc.      They   can    be   made    easily   and   cheaply. 


RECORDING    HEART    TRACINGS 


67 


starts  just  to  the  right  of  the  seam  in  the  drum  paper.  The 
time  marker  can  be  arranged  and  the  time  recorded  as  the 
record  of  the  heart  beat  is  taken,  or  the  time  record  may 
be  put  on  after  the  heart  tracings  are  finished  if  the 
speed  of  the  drum  is  approximately  constant.  This  latter 
procedure  is  advisable  for  the  first  few  records.  It  is  also 
advisable  to  use  a  signal  magnet  in  the  primary  circuit  ar- 
ranged in  such  a  manner  that  the  exact  moment  and  the 


Fig.    63. — Arrangement    of    apparatus    for    recording    frog    heart    tracings    by    the    sus- 
pension  method.      The   wires   from   the   signal    magnet    are   connected   with   the    time    clock. 

duration  of  the  stimulation  may  be  recorded  directly  be- 
neath the  writing  point  of  the  heart  lever.  The  heart  trac- 
ing should  have  an  amplitude  of  about  one-half  to  one 
inch.  The  drum  should  have  a  slow  or  medium  speed.  If 
the  Harvard  drums  are  used  it  is  often  advisable  to  clamp 
a  folded  piece  of  paper  on  to  the  largest  fan  to  thus  fur- 
ther slow  the  speed.  It  may  be  necessar}^  to  put  a  small 
weight  on  to  the  long  end  of  the  heart  lever  to  secure  the 
desired  amplitude  of  movement  for  the  tracing. 


bo  EXPERIMEISTTAL   PHARMACOLOGY 

When  all  adjustments  are  made  start  the  drnm  and  take 
a  ^'normal''  tracing.  When  about  two  inches  of  this  has 
been  recorded  then  stimulate  the  vagus  nerve  and  get  a 
record  of  the  normal  inhibition.  It  is  important  that  the 
electrodes  do  not  rest  on  the  neck  or  thoracic  muscles  of 
the  frog,  for  if  such  is  the  case  these  muscles  will  contract 
when  the  current  is  turned  on  and  the  frog  will  move  thus 
spoiling  the  appearance  of  the  tracing.  Do  not  stop  the 
heart  longer  than  is  necessary  (2  or  3  beats).  Then  allow 
the  heart  to  recover  (the  drum  is  kept  running)  from  the 
inhibition  and  record  another  two  inches  of  "normal" 
tracing.  Then  stimulate  the  vagus.  This  gives  an  oppor- 
tunity to  secure  two  sets  of  records. 

Now  back  the  drum  away  from  the  writing  lever  a  little 
and  turn  it  back  to  the  starting  point.     Lower  the  drum 


Fig.    64. — Me(;licine    dropper    for    applying    solutions    to    the    heart. 

so  that  the  next  round  of  the  tracing  will  be  about  one- 
half  inch  above  the  first.  Pull  the  drujn  forward  and 
start  it  again  and  when  about  one  inch  of  tracing  has  been 
recorded  then  drop  on  to  the  heart  with  a  medicine  dropper 
(Fig.  64)  five  or  six  drops  of  a  saturated  solution  of  ether  in 
normal  salt  solution  (solubility=l  to  9).  AVhen  the  tracing 
again  comes  directly  over  the  place  where  the  vagus  was 
stimulated  in  the  lower  tracing  stimulate  the  vagus  again 
and  determine  whether  or  not  the  drug  has  affected  the 
reaction  of  the  heart  to  the  inhibition.  Now  rapidly  drop 
more  ether  solution  on  the  heart  and  repeat  the  vagus 
stimulation  directly  over  the  second  inhibition  record  in 
the  normal  tracing.  Keep  dropping  on  the  drug  and  note 
carefully  the  effect  on  the  rate  and  amplitude  of  the  heart. 
Observe  the  appearance  of  the  auricles  and  ventricles.  Can 
you  determine  in  your  tracing  those  portions  of  the  rec- 
ord mjade  by  the  sinus,  auricular,  and  ventricular  contrac- 


RECORDING    HEART    TRACINGS 


69 


tions  respectively?    In  which  direction  does  the  lever  move 
in  systole? 

Take  several  rows  of  tracings,  lowering  the  drum  suf- 
ficiently to  leave  about  three-eighths  or  one-half  inch  be- 
tween each  row  of  tracings.  The  record  should  thus  read 
from  left  to  right  and  from  bottom  to  top.  As  the  ether 
is  dropped  on,  the  action  on  the  systole  of  the  heart  will 
soon  become  apparent.  This  should  progress  until  the 
heart  almost  stops.  Then  irrigate  the  heart  mth  normal 
salt  solution  a  while  and  see  if  you  can  get  it  to  recover. 
Stimulate  the  vagus  from  time  to  time  and  see  if  the  power 


/  Carohd  Arch 


Ritjht 

Systemic-^ 
arch 

Ei(jht  Pulmo 

ci/faneoiys  arch 


ni^hi  Auricle  ^      / 
Truncus  arteriosusS 


Ventricle 


Ttiahi  Auricle 
'-LeftAnfXamI 

-Left  Auricle 
Pulmonary  Vein   ' 


Biqht  Carotid 
/  arch 

Kiqht  Systemic 
arch 

niotit  Puiwo- 

cuhneous  arch 

Right  Ant 
Cetval  Vein 

'^Openinq  of 
Sinus  venosus 
ink)  the  Eight 

Auricle 

~Sinu5  venosus 


Fig. 


Posh  Csvd  vein 

-The   anatomy   of   the   frog's   heart.      (Modified    from   Wiedersheim.) 


of  inhibition  is  lost.  How  has  the  drug  affected  the  heart? 
Is  the  innervation  of  the  organ  involved  in  the  action  or 
is  this  mainly  a  muscular  affair?  Does  this  experiment 
show  any  action  of  the  drug  on  the  cardio-inhibitory  center 
in  the  medulla  ?  AVhen  the  heart  tracings  are  finished  then 
record  the  time  in  five  second  intervals  in  two  or  three 
rounds  on  the  drum.  These  time  records  also  serve  as 
comparison  lines  to  determine  whether  or  not  there  has 
been  an  increase  or  a  decrease  of  tone  in  the  heart  muscle. 
What  effect  Avould  a  decrease  in  heart  muscle  tone  have 
on  the  position  of  the  record  with  reference  to  a  horizontal 
line  draA\m  around  the  drum? 


70 


EXPERIMENTAL   PHARMACOLOGY 


Chloroform.     (Action  on  the  Frog's  Heart.) 

2.  Eepeat  the  above  experiment  on  a  fresh  frog  using  a 
saturated  solution  of  chloroform  in  normal  salt  solution 
(solubility =1  to  200).  Does  chloroform  affect  the  nervous 
inhibiting  apparatus  of  the  heart  ?  What  differences  do  you 
note  between  ether  and  chloroform  as  regards  their  cardiac 
action  I 

3.  Familiarize  yourself  with  the  anatomy  of  the  frog's 
heart  (Fig.  65).  How  does  the  frog's  circulatory  apparatus 
differ  from  that  of  a  mammal? 


Dorsal. 


Ventral. 


LH  •  pc 


l\mph  hesri ., 


Fig.   66. — Diagrammatic   representation   of  the  lymph  spaces   of   the   frog. 
(Modified   from    Ecker.) 


Chloroform.     (Action  on  Lymph  Hearts.) 

4.  Allow  a  frog  to  sit  in  a  good  light  with  the  lower  end 
of  the  urostyle  turned  toward  a  window.  On  each  side  of 
the  lower  end  of  the  urostyle  {L.H.  in  Fig.  QQ)  note  a  series 
of  feeble  pulsations  beneath  the  skin.  This  is  caused  by 
the  beating  of  the  posterior  pair  of  lymph  hearts.  (The 
anterior  pair  of  lymph  hearts  are  located,  one  heart  on 
each  side,  between  the  transverse  processes  of  the  third 


ACTION    OF   ETHER   ON   THE    HEART  71 

and  fourth  vertebi'ce.  Their  heats  cannot  he  ohserved  from 
the  exterior.)  Count  the  rate  of  lymph  heart  beats  and 
also  the  rate  of  the  blood  heart  beats.  (These  can  be  seen 
beneath  the  skin  of  the  chest.)  If  the  frog  breathes  also 
count  the  rate  of  respiration.  (How  does  a  frog  breathe?) 
Now  place  the  frog  under  a  battery  jar  and  deeply  anes- 
thetize it  with  chloroform.  Kemove  the  animal  and  again 
count  the  rate  of  beats  of  the  heart,  of  the  posterior  lymph 
hearts  (do  these  beat  synchronously  1 ) ,  and  the  rate  of 
respiration.  AVhat  conclusions  can  you  drawl  Are  these 
results  due  to  a  central  or  a  peripheral  action  of  the  chloro- 
form! (How  is  the  beating  of  the  lymph -hearts  controlled? 
How  is  this  mechanism  j)rovided  for  in  the  mammal?)  Al- 
low the  frog  to  recover  and  observe  its  symptoms.  How 
long  before  the  frog  becomes  normal  again? 

EXPERIMENT  III. 

Turtle:    Vag-us  Dissection.    (Action  of  Ether  on  the 

Heart.) 

1.  Pick  up  a  turtle  and  draw  its  head  forward  out  of  the 
shell.  This  may  be  done  with  a  wire  having  a  short  sharp 
hook  on  one  end.  The  hook  is  passed  between  the  carapace 
and  plastron  and  hooked  into  the  anterior  angle  of  the 
lower  jaw  below.  Draw  out  the  head  and  seize  it  between 
the  first  and  second  fingers  of  the  left  hand.  Clasp  the 
hand  around  the  turtle's  neck  and  pith  it  with  a  sharp 
probe  or  hat  pin  in  the  same  way  that  the  frog  is'  pithed. 
It  is  advisable  to  pith  the  cord  also  by  pushing  a  soft  brass 
or  iron  wire  down  the  spinal  canal.  The  wire  is  intro- 
duced through  the  same  opening  by  which  the  animal's 
brain  was  destroyed. 

Catch  the  turtle's  lower  jaw  in  the  hook  of  a  turtle  board 
(Fig.  28)  in  the  manner  shown  in  Fig.  67.  Pull  the  hind 
legs  outward  and  backward  firmly  and  forcibly  and  fasten 
them  to  the  board.    This  may  be  done  with  strings  (hea^^'') 


72 


EXPERIMEiSTTAL   PHARMACOLOGY 


as  shown  in  Fig.  67,  but  it  can  be  done  quicker  and  per- 
haps better  by  long  sharp  iron  tacks  which  are  driven 
through  the  feet  and  into  the  turtle  board  with  a  hammer. 


Fig.  67. — Arrangement  of  apparatus  for  recording  turtle  heart  tracings  by  the  sus- 
pension method.  Note  that  only  a  small  square  opening  is  made  in  the  plastron  over 
the   heart. 


It  is  very  important  that  the  animal  he  fully  stretched  out 
so  that  it  cannot  move  reflexly  and  spoil  the  tracings  later. 
Next  pull  out  laterally  the  fore  limbs  and  fasten  them  down 
firmly. 


EXPOSING  THE   TURTLE  S  HEART 


73 


Now  by  means  of  a  liand  bandage  saw  (Fig.  104),  or  with 
a  circular  saw  on  a  small  motor  (Fig.  68),  cut  out  a  square 
opening  in  the  plastron  over  the  heart  as  shown  in  Fig. 
67.  With  a  scalpel  handle  pry  up  the  square  piece  of 
plastron  and  then  carefully  strip  loose  the  tissues  below 
the  square  so  as  to  avoid  hemorrhage.  There  should  be 
practically  no  bleeding.  With  scissors  cut  away  the  peri- 
cardium and  expose  the  heart.  Familiarize  yourself  with 
the  anatomy  of  the  turtle's  heart  (Fig.  69). 

In  the  side  of  the  neck  make  a  longitudinal  incision  and 


Circular     ^P'1^^^ . 
_53jy «  extension 


Fig.  68. — Method  of  sawing  ^ut  a  square  in  the  plastron  of  a  turtle  by  means  of 
a   circular   saw    (3   inches   in   diameter)    attached   to   a   small    (1/10   horse   power   motor). 

expose  the  carotid  artery,  the  vagus  nerve,  and  the  sym- 
pathetic nerve  (Fig.  70).  To  identify  the  vagus  nerve  place 
a  thread  around  it  loosely,  lift  up  the  thread,  and  with  a 
moderately  strong  tetanizing  current  stimulate  the  nerve. 
Does  the  heart  stop  beating!  If  not,  strengthen  the  cur- 
rent. The  heart  normally  should  entirely  cease  to  beat 
when  the  vagus  nerve  is  stimulated  with  a  sufficiently  strong- 
current. 

Arrange  the  turtle  and  apparatus  to  record  a  heart  trac- 
ing as  shown  in  Fig.  67.  It  may  be  desirable  to  use  the 
signal  magnet  in  the  primary  current  for  the  induction  coil 


74  experimejsttal  pharmacology 

and  thus  let  the  signal  magnet  record  the  moment  and  du- 
ration of  stimulation  rather  than  the  time.  After  the 
heart  records  have  been  secured  then  the  time  tracing  (in 
five  second,  etc.,  intervals)  can  be  put  on  the  drum.  The 
electrodes  should  be  adjusted  under  the  vagus  nerve  in 
such  a  way  that  they  need  not  be  disturbed  or  moved  in 
any  way  when  one  desires  to  stimulate  the  nerve.  Keep 
the  nerve  moist  with  normal  salt  solution.  The  record 
should  be  made  in  such  a  manner  that  it  will  read  from 
left  to  right  and  from  bottom  to  top.  The  amplitude  of 
the  beats  should  be  about  one  inch.  The  drum  should  turn 
at  a  moderately  slow  speed.  When  all  adjustments  of  the 
apparatus  are  completed  record  about  one  or  two  inches 
of  the  normal  tracing  and  then  stimulate  the  vagus  nerve. 
The  right  nerve  usually  is  more  effective  in  stopping  the 
heart  than  is  the  left.  Allow  the  heart  to  recover  (the 
drum  should  be  kept  going  all  the  time)  and  when  about 
one  or  two  inches  more  of  normal  record  have  been  ob- 
tained, stimulate  the  vagus  (or  the  opposite  vagus)  again 
and  thus  get  two  sets  of  records.  If  there  are  three  stu- 
dents in  the  group  it  is  often  advisable  to  thus  make  three 
sets  of  records  so  that  each  student  can  have  one.  The 
cardiac  inhibitory  poAvers  of  the  vagi  in  the  turtle  are  not 
nearly  so  easily  exhausted  by  electrical  stimulation  as  are 
those  of  the  frog. 

When  enough  normal  tracings  have  been  secured  lower 
the  drum  so  that  about  one-half  inch  will  be  left  between 
the  first  round  of  the  record  and  the  second  and  start  over 
from  the  beginning  (left  hand  side)  of  the  record  again. 
When  the  second  record  reaches  a  point  about  one  inch 
to  the  left  of  the  place  where  the  vagus  nerve  was  stimu- 
lated in  the  first  round  then  rapidly  drop  ten  drops  of 
a  solution  of  ether  in  salt  solution  on  the  heart  as  was 
done  with  the  frog's  heart  in  Experiment  II  (1).  A¥hen 
the  record  comes  directly  over  the  place  where  the  vagus 
nerve  was  stimulated  in  the  first  round  of  the  tracing  stim- 


Carotid  art  1 

im 

Cdrofid  drt. 

Subd&v.  ^rt-  ^^^ 
Pulmo.  ^rt^^^^^ 

^^^^^F^ 

i'Sup. 

Subcldvisn  art 
Venae  csvee. 
^^^       Pulmonary  drt 

Pulmo.Q^     ^    /'          ] 
vein  \^^^''^{  f 

m 

P^"    ^^^Pu/nT^B[^ 

nt  Auricle  -^M^^^_^ 

■^If^M  Lft  Auricle 

Inf.  Ke/)a  cai/a        ^^ 

L    ventricle 

m 

/?/:  Aortic  srch  — ^ 

V 

i 

Coeliac  arteries 

1 

-Dorsal  Aort^            ^,/^^c^ 

Fig.   69. — Diagrammatic  representation   of  the   turtle's   heart.      (Modilied   from   Nuhn.) 


INNERVATIOISr   OF  THE  TURTLE  S  HEART 


iO 


Testudo  qraecd         Specimen  A 


Fig.  70. — Schematic  representation  of  the  vagus  and  sympathetic  nerves  in  a  turtle 
(testudo  graeca).  (Modified  from  Gaskell.)  \'ariations  in  the  arrangement  of  the 
sympathetic  fibers  were  frequently  found  by  Gaskell.  (The  writer  has  seen  no  instance 
in  which  the  arrangement  and  connections  of  the  sympathetic  fibers  existed  as  shown  in 
this  illustration,  but  the  general  plan  of  distribution  appears  to  be  approximately  the 
same    in    all    specimens.) 


76  EXPERIMENTAL   PHARMACOLOGY 

ulate  the  same  nerve  again  with  the  same  strength  of  cur- 
rent and  determine  whether  or  not  the  nervous  inhibitory 
mechanism  has  been  affected  by  the  ether.  Is  the  ampli- 
tude, the  rate,  or  the  tone  of  the  heart  affected?  If  the 
tone  of  the  muscle  is  loAvered  how  will  this  affect  the  trac- 
ing? (After  the  records  are  all  obtained,  draw  two  or 
three  parallel  lines  around  the  drum  by  rotating  it  against 
the  writing  point  of  a  stationary  signal  magnet  or  tam- 
bour. By  comparing  the  general  rise  or  fall  of  a  whole 
round  of  heart  beats  with  this  constant  line  any  change  in 
muscular  tone  will  be  observed  at  once.) 

Apply  ether  solution  to  the  heart  rapidl}^  ond  at  the 
proper  position  stimulate  the  vagus  nerve.  Take  several 
rounds  of  the  tracings  (lowering  the  drum  a  suitable  dis- 
tance between  each  two  rounds)  and  observe  the  continued 
action  of  the  drug  on  the  heart.  Does  the  vagus  nerve  be- 
come more  or  less  effective  in  stopping  the  heart?  How 
do  you  explain  this  action?  The  drum  may  be  stopped  for 
a  while  at  the  end  of  each  round  if  the  changes  in  the  heart 
come  on  very  slowly. 

When  the  heart  has  almost  stopped,  then  proceed  to  rap- 
idly wash  off  the  ether  with  warm  normal  salt  solution. 
See  if  you  can  get  the  heart  to  recover.  How  do  you  ex- 
plain any  peculiar  rises  and  falls  in  the  general  contour 
of  your  tracings?  How  can  you  prevent  these  in  later  rec- 
ords?   Were  you  warned  about  this  before? 

Chloroform.     (Action  on  the  Turtle's  Heart.) 

2.  Repeat  the  above  experiment  on  a  fresh  turtle  using 
a  saturated  solution  of  chloroform  in  tap  water  saline. 
Does  the  chloroform  affect  the  nervous  inhibitory  apparatus 
of  the  heart?  What  difference  do  you  note  between  ether 
and  chloroform  as  regards  their  cardiac  action? 


ETHER,    CHLOROFORM,   ETHYL    BROMIDE 


a 


EXPERIMENT  IV. 

Ether,  Chloroform,  Ethyl  Bromide.     (Dog:     Respiration, 
Blood-pressure,  Cervical  Vagi,  and  Sympathetics.) 

1.  (a)  Read  the  following  directions  over  very  carefully 
at  least  once  before  starting  the  experiment.  It  is  exceed- 
ingly important  that  you  learn  the  proper  technic  for  the 
following  procedures  correctly  at  the  start.  Arrange  the 
table  for  the  experiment  as  shown  in  Eig.  117. 

Anesthetization  of  the  Animal. — (a)  Treat  the  dog- 
gently  and  kindly  and  do  not  irritate  or  frighten  it.    Two 


Fia 


71. — Method    of    etherizing    a    dog.      The    animal    sliould    not    be    frightened    or 
hurt.      (For   description    see   text.) 


(or  three)  students  should  apply  the  anesthetic.  The  ani- 
mal is  caught  by  the  head  and  legs  and  gently  placed  on 
its  left  side  {ivhy  left?).  If  the  animal  is  vicious  it  should 
be  muzzled  at  the  start.  The  anesthetizer  seizes  the  head 
gently  but  firmly  and  lays  it  down  on  a  towel  which  has 
already  been  placed  flat  on  the  floor  (Fig.  71).  The  head 
is  held  by  the  right  hand  and  the  ends  of  the  towel  are 


78  EXPERIMENTAL    PHARMACOLOGY 

brought  up  separately  and  wrapped  about  the  head.  The 
right  hand  then  carefully  seizes  the  towel  and  holds  it 
tightly  around  the  neck  of  the  dog.  The  towel  thus  forms 
a  kind  of  sack  or  tube  around  the  dog's  head.  The  distal 
end  of  this  sack  is  now  seized  with  the  anesthetizer's  left 
hand  and  twisted  around  two  or  three  times  and  then  placed 
flat  on  the  floor  where  it  is  held  dowu  firmly  with  the  anes- 
thetizer's left  foot.  Both  the  anesthetizer  and  the  assist- 
ant should  stand  behind  the  dog.  (Why?)  The  assistant 
reaches  forward  over  the  animal  and  holds  both  fore  feet 
in  the  left  hand  and  the  hind  feet  in  the  right  hand.  To 
prevent  the  dog  from  getting  up  the  anesthetizer  holds  its 
head  firmly  down  to  the  floor  with  his  right  hand  and  the 
assistant  places  one  (or  both)  knees  on  its  body.  If  the 
dog  is  muzzled,  two  students  can  thus  control  almost  any 
dog  with  but  little  trouble.  (In  practice  one  seldom  muz- 
zles the  dog.) 

Caution. — There  should  always  be  kept  in  plain  view  and  in  easy  reach 
in  the  laboratory  a  bottle  of  carbolic  acid  solution  and  a  bottle  of  alcohol. 
These  should  be  kept  together  and  a  toothpick  with  a  little  cotton  wrapped 
around  one  end  should  be  stuck  in  the  cork  of  the  carbolic  acid  bottle.  One 
never  knows  when  a  student  may  be  bitten  by  a  dog,  and  as  all  dogs  or  cats 
are  subject  to  rabies,  any  wound  made  by  the  animal's  teeth  or  claws  should 
be  cauterized  with  carbolic  acid  immediately.  This  is  done  by  wetting  the 
cotton  on  the  toothpick  with  the  acid  and  applying  it  to  the  wound.  In  a 
few  seconds  the  acid  will  penetrate  the  tissues  as  deeply  as  the  virus  has 
probably  gone  and  then  the  acid  should  be  carefully  washed  off  with  the  alco- 
hol. This  dissolves  out  the  acid  and  removes  it.  The  acid  may  cause  the 
tissues  to  take  on  a  whitish,  cooked  appearance,  but  the  alcohol  often  removes 
this  entirely.  Do  not  Mil  the  anivial  if  the  wound  appears  at  all  dangerous. 
Save  it  carefully  for  diagnostic  purposes.  Consult  a  first-class  bacteriologist 
or  the  city  health  department. 

As  shown  in  Fig.  71  the  anesthetizer  now  drops  some 
ether  on  the  towel  in  front  of  the  animal's  nose.  The  dog 
will  struggle  some  and  should  be  held  firmly.  With  suf- 
ficient ether  the  animal  should  be  anesthetized  in  about 
two  minutes.  Be  sure  the  dog  gets  sufficient  air  through 
the  towel.    Watch  the  respiration  closely.    The  animal  will 


ANESTHETIZATION    OF    ANIMAL 


7iJ 


likely  hold  its  breath  at  the  start.  The  danger  signal  af- 
ter this  preliminary  holding  of  the  breath  is  stoppage  or 
great  shalloivness  of  the  respiration.  Avoid  this  carefully. 
When  the  limbs  become  limp  and  drop  down  flaccidly  when 
lifted  and  turned  loose  then  touch  the  cornea  gently  and 
see  if  the  dog  winks.  If  not,  hastily  place  it  on  a  dog  board 
on  the  table  *(Figs.  20  and  72).  The  animal's  head  is  quickly 
draw^i  forward  between  the  upright  posts  and  the  rod  is 
pushed  through  between  the  teeth   (just  behind  the  long 


Fig.  72. — Ivaboratory  table.  The  top  of  the  table  is  5yi  feet  long  and  33  inches 
wide.  The  height  is  35  inches.  The  small  square  stand  at  the  head  of  the  table  is  13 
inches  square  at  the  top  and  has  a  small  (7  inches)  round  sink  in  the  center.  Gas 
(G),  air  (A)  (positive  or  negative  pressure,  constant  or  interrupted  current),  hot  (H  W) 
and  cold  (C  W)  water,  inductorium  or  battery  current  (B),  clock  current  (T),  and 
drop  light  circuit  (Z,)  are  all  connected  with  the  (immovable)  square  stand.  The  piping 
for  the  water,  electricity,  etc.,  runs  in  the  floor.  One  locker  and  one  large  drawer 
are  available  on  each  side  of  the  table.  The  dog  board  is  in  position  on  the  table. 
The  sink,   etc.,   should  be   at  the   end   of   the   table   toward   the   window. 


canines).  A  heavy  twine  about  sixteen  inches  long  should 
have  been  previoush^  laid  across  the  board  just  back  of 
the  upright  posts.  When  the  rod  is  pushed  in  this  twine 
is  then  ready  to  be  brought  up  at  once  and  tied  as  tightly 
as  possible  around  the  dog's  mouth  just  hacJx  of  the  rod. 


80 


EXPERIMENTAL   PHARMACOLOGY 


Fig.    75. — Metronome  for  operating  the   electric  time   signal. 


Fig.    74. — L,ieb-Becker   time    marker    made    from    an    Ingersoll    watch.  Time    intervals 

■of    1    second,    5    seconds   or    1    minute   may  be  recorded.      Obtainable    from  Mr.    J.    Becker, 

Terrace  Avenue,   Maywood,   N.   J.      Price   $5.50.      (See   C.    C.    Lieb:    Jour,  of   Pharm.    and 
JJxper.    Therapeutics,    1917,    9,    227.) 


ANESTHETIZATIOISr    OF    AISTIMAL 


81 


The  operator  uses  both  hands  to  draw  this  string  tight, 
and  when  the  first  knot  is  tied  the  assistant  places  his  right 
thumb  over  the  knot  to  hold  it  tightly  while  the  second 
knot  is  tied.     Why  should  this  string  be  tied  so  tightly? 


Fig.    75. — Harvard    time    clock. 


The  average  student  will  probabh?'  find  out  before  the  first 
experiment  is  finished.  The  toAvel  is  now  quickly  tucked 
down  over  the  dog's,  mouth  and  nose  and  a  little  ether  is 
poured  on.     The  most  steady  and  reliable  student  in  the 


82 


EXPEKIMENTAL   PHARMACOLOGY 


Fig.  Id. — Jaquet  chronograph  (records  in  intervals  of  1/5  second  and  1  second). 


Fig.  "jj, — Two  forms  of  time  clocks.  (Both  made  by  E-  Zimmermann,  lycipzig  and 
Berlin.)  The  large  clock  (Bowditch-Baltzar)  marks  intervals  of  1,  2,  3,  4,  S,  10,  15, 
20,    30   and   60   seconds. 


ARRANGING  FOR  OPERATION 


group  now  takes  charge  of  the  anestlietic  and  henceforth 
directs  Ms  attention  solely  to  this  ivorh.  Quickly  slip  the 
cords  (each  of  which  has  a  slip  noose,  Fig.  79)  over  the 


Fig.    78. — Method   of  fastening   the   animal's   head   to   the    dog   board. 


Fig.    79. — Heavy   string   with   slip   noose   ready   to    put   around   the   fore   limb. 

fore  legs  up  to  the  elbows  (Fig.  80).  Draw  these  cords 
tightly  and  then  wrap  the  ends  around  the  screw  eyes  at 
the  edge  of  the  dog  hoard  (Fig.  81.)     After  the  third  or 


84 


EXPERIMENTAL   PHARMACOLOGY 


fourth  round  draw  the  end  of  each  cord  in  between  the 
screw  eye  and  the  edge  of  the  board.     This  will  usually 


Fig.    80. — Method   of   attaching   fore   limbs   to   the   dog   board. 


Fig.   81.— Method   for  quickly  fastening  the  string  to   the   board   without  tieing  any  knots. 

hold  tightly  and  saves  tying  any  knots  which  should  be 
avoided  if  possible.  Stretch  out  the  hind  legs  and  tie  them 
down  as  shown  in  Fig.  82. 


PRELIMINARY    OPERATIONS  oO 

(b)  Insertion  of  Tracheal  and  Carotid  Cannulas;  Isola- 
tion of  Vagi  and  External  Jugular  Vein. — As  soon  as  the 
animal  is  securely  fastened  doA\ai,  a  median  incision  is 
made  in  the  skin  and  fascia  over  the  trachea  as  shoA\m  in 
Fig.  83.  Observe  with  great  care  the  technic  shown  in  the 
ilhistration  and  follow  it  carefully.    Next  take  two  aneurism 


Fig. 


-Method    of    fastening   the    hind    limbs. 


needles  and  separate  the  mesial  borders  of  the  sternohyoid 
muscles  as  shown  in  Fig.  84.  This  brings  into  view  the 
trachea  (Fig.  85)  with  the  carotid  sheath  containing  the 
carotid  artery  and  vago- sympathetic  nerves  on  each  side 
(posteriorly)  of  the  wind-pipe.  Next  take  an  aneurism 
needle  and  hook  it  under  the  trachea  as  shown  in  Fig.  86. 
With  the  largest  forceps  pick  up  by  one  end  the  hea^^^ 
twine  to  tie  in  the  tracheal  cannula.  While  holding  this 
in  the  forceps  lift  up  the  trachea  with  the  aneurism  needle 
and  push  the   forceps    (holding  the   t^^^.ne)    through  the 


EXPERIMENTAL   PHAEMACOLOGY 


fascia  back  of  the  trachea.  About  half  the  length  of  the 
forceps  is  pushed  through  below  the  trachea  and  the  for- 
ceps are  thus  left  in  place  to  hold  up  the  trachea.  The  end 
of  the  twine  is  taken  out  of  the  forceps  and  the  twine  is 
drawn  through  a  little  over  half  its  length  (Fig.  87).    The 


Lefi  hand  of 


l.^fih6nd  of 
/Issisfani: 


Knife  in  'Ki.H^nd  of 

Op<?rait>r 
Incist'on  -thru  skin  s/ 
Tascia  fo  Muscle. 


-Method   of   incising  the   skin    over   the   trachea. 


twine  is  then  tied  loosely  and  with  scissors  the  trachea  is 
cut  crossivise  about  three-fourths  in  two  (Fig.  87).  With 
large  sharp-pointed  forceps  the  operator  (right  hand)  now 
holds  open  the  cut  portion  of  the  trachea  while  the  assist- 
ant (right  hand)  pushes  in  the  tracheal  cannula  (Fig.  88). 
This  is  at  once  tied  in  and  connected  with  the  ether  bottle 


PRELIMINARY    OPERATIONS 


87 


rig.     84. — Separation    of    the    borders     of    the    sternohyoid    muscles     with    two    aneurism 

needles. 


Cefro^id.  sheaf h 
Conf-aininq  ygao- 


gfheiic  ner^e 


5ympgrh&ric  nen^e 
^  Caroh'd  earfery 

M.  Sferno-hyoideus 


^*>V^- 


Pig.    85. — The    trachea    is    exposed    and    the    carotid    sheath    is    seen    just    to    the    postero- 
lateral  border   of   the  windpipe. 


EXPERIMENTAL   PHARMACOLOGY 


Fig.    86. — An   aneurism   needle   is   used   to   lift   up   the   trachea   while   the    forceps    (holding 
the  end   of  a  heavy   string)    are  passed  beneath  the  trachea. 


Cu(i  Trachea 
3/^  fhru,  cross- 
wise, i>e/*ree/? 
n'nqs. 


Shincj  loosely 
tied  onfrache.. 


B'^ig.    87. — The   string   is   tied  loosely   and   the   forceps   are   left   in    position   to    hold   up   the 
trachea  which  is  cut  crosswise  about  three-fourths  in  two  with  the  scissors. 


PKELIMINARY    OPERATIONS 


89 


Fig.    88. — Insertion   of   the   tracheal   cannula. 


M  Caroiid  arkr\j  d-  f,(7) 
V^fus  tfer/e-      y\  \^^ 

bluni  poirrhed  C=^^^^ 

probe.    Doni  use  hni^ 


Fig.   89. — Lifting  up   the   right   carotid   sheath   on   an  aneurism    needle.      A   blunt   probe   is 
then  vised  to  separate  the  vago-sympathetic  trunk  from  the  artery. 


90 


EXPBKIMEE^TAL   PHAEMACOLOGY 


Loose  liaahre, 
TIace  on  wiirh  forceps^ 
NOT  v/ifh  fin(^e.  ~^  '~~ 


Liaai'ure  on   Vaqo 
sympafhefic  nerve 


loose  Licj.  arouvdarhr^- 
Tisce  ov  yriih  forceps,  W/A...... 

/YOT  ty/H  f infers  ^    ^^^ 


Fig.   90. — Ligation   of   the   carotid    (in  two   places)    and   vago-sympathetic   nerve. 


/Issisfj/ii- 


Fig.  91. — Opening  the  carotid  artery.  (The  incision  should  be  made  nearer  to  the 
upper  ligature  and  the  scissors  should  point  more  toward  the  heart  than  the  picture 
indicates.) 


PRELIMINARY    OPERATIONS 


91 


Fig.   92. — Insertion   of  the  arterial  cannula.      The  cannula   and   tubes  contain  no   solution; 
this  is  run  in  later  after  the  cannula  is  firmly   tied   into   the   artery. 


Pos/hon  of  ExtJuaulsr  V. 


Fig.  93. — The  cannula  is  tied  into  the  artery.  The  right  external  jugular  vein  is 
dissected  out  by  pulling  the  skin  outward  while  the  muscles  and  fascia  are  scraped 
back  inward  with   the   probe.      The  vein  lies  in   the   fascia   as  indicated. 


92  EXPEKIMENTAL   PHARMACOLOGY 

and  the  screw  clamp  on  the  straight  end  of  the  cannula  is 
adjusted  to  make  the  dog  breathe  just  enough  ether  to  keep 
the  anesthesia  constant  (Fig.  89).  The  forceps  beneath 
the  trachea  are  withdrawn  and  the  aneurism  needle  is 
hooked  under  the  right  carotid  sheath  which  is  lifted  up 
out  of  the  wound  (Fig.  89).  With  a  hlunt-pointed  probe 
the  sheath  is  opened  and  the  carotid  artery  and  vago-sym- 
pathetic  trunk  are  separated.  A  ligature  is  placed  under 
the  nerve  and  tied  loosely.  A  bull-dog  clamp  is  placed  on 
the  ends  of  this  ligature  (Fig.  90)  which  is  now  dropped 
down  beside  the  neck.  Similarly  with  forceps  two  more 
ligatures  are  placed  on  the  carotid  artery  and  tied  loosely 
(Fig.  90).  It  is  extremely  important  that  the  student  learn 
to  do  these  operations  ivitJi  his  dissecting  instruments — 
not  ivitJi  his  fingers  except  to  tie  knots,  etc.  Many  stu- 
dents bring  with  them  from  their  anatomy  courses  an  ab- 
surd notion  that  they  should  do  most  of  their  dissections 
with  their  fingers.  Learn  to  use  your  dissecting  instru- 
ments. That  is  the  only  royal  road  to  first-class  operative 
success.  Place  a  bull-dog  clamp  (serrefin)  on  the  carotid 
low  down  in  the  neck  and  tie  tightly  the  upper  ligature. 
The  lower  ligature  lies  close  to.  the  bull-dog  (Fig.  91). 
Place  the  scissors  ready  to  cut  the  artery  about  half  in 
two  at  a  point  just  heloiv  the  upper  ligature.  (Why  here?) 
The  assistant  holds  a  piece  of  cotton  just  over  the  end  of 
the  scissors  to  catch  any  blood  that  may  fly  out  of  the  seg- 
ment of  artery  as  the  operator  cuts  with  the  scissors  (Fig. 
91).  With  the  large  sharp-pointed  forceps  the  operator 
now  holds  open  the  artery  while  the  assistant  pushes  in 
the  arterial  cannula  (Fig.  92)  which  is  already  connected 
with  the  manometer.  The  washout  tube  and  clip  are  also 
on  the  side  tube  of  the  cannula.  There  is  no  fluid  in  the 
cannula  or  tube  connecting  it  to  the  manometer.  This  fluid 
is  rmi  in  later  ivhen  the  operation  at  the  neck  is  complete. 
If  the  tip  of  the  cannula  does  not  enter  the  artery  readily 
the  cannula  should  be  dipped  into  a  beaker  of  water  and 
then  inserted  into  the  artery.    This  is  the  usual  method  to 


PRELIMIlSrARY    OPERATIONS 


93 


get  a  cannula  into  a  vessel.  The  cannula  is  now  tied  in 
tlie  artery  (Fig.  93).  (If  desired  for  injections  the  right 
external  jugular  vein  may  also  be  dissected  out  just  be- 
neath the  skin  and  fascia  of  the  neck — Fig.  93.) 

In  a  similar  manner  isolate  and  ligate  loosely  the  left 
vagus  nerve. 

(c)  Insertion  of  Femoral  Injecting  Cannula;  Dissection 
of  Femoral  Artery  and  Vein  and  Saphenous  Nerve. — Ob- 


masm^ 


Fig.    94. — Burette,    tubing,    clips    and    cannula    arranged    for    connecting    with    a   vein    for 

injection   of   drugs. 


serve  with  great  care  the  arrangement  of  the  apparatus 
shown  in  Fig.  94.  Solutions  to  be  injected  into  the  veins 
are  placed  in  the  burette.  The  cannula  is  tied  in  the  vein, 
a  bull-dog  clamp  being  always  left  on  the  vein  just  prox- 
imal to  the  cannula.  When  injections  are  made  the  bull- 
dog is  loosened  and  the  dose  is  measured  by  opening  cau- 
tiously the  clip  on  the  tube  leading  from  the  burette.  As 
soon  as  the  drug  is  injected  the  spring  clip  is  closed  and  the 
bull-dog  is  replaced  on  the  vein.     This  is  a  double  check 


94  EXPERIMENTAL   PHARMACOLOGY 

for  safety  to  prevent  the  unintentional  injection  of  drugs. 
This  cannula  is  exactly  similar  to  the  one  in  the  carotid 
artery.  Drug  solutions  in  the  burette  can  be  changed 
quickly  by  running  the  solution  out  at  the  side  (wash-out) 
tube.  The  burette  is  then  rinsed  with  water  and  the  sec- 
ond drug  is  poured  into  the  burette.  To  get  the  air  out 
of  the  tubing  the  two  clips  are  opened  a  little  and  some 
of  the  drug  solution  is  washed  out  at  the  side  tube.  The 
solution  is  caught  in  a  beaker  and  returned  to  the  burette. 

When  the  burette  is  to  be  inserted  at  first  some  normal 
salt  solution  should  be  placed  in  the  burette  and  a  little 
of  it  run  through  the  cannula.  This  wets  the  inside  of  the 
cannula  (and  tubes)  and  prevents  air  bubbles  from  stick- 
ing inside  the  cannula  later  on  when  the  drug  is  poured  in. 
Just  as  the  cannula  is  inserted  into  the  vein  some  of  this 
salt  solution  is  run  out  and  the  end  of  the  vein  next  to  the 
cannula  is  thus  filled  with  solution  and  the  air  is  driven 
out.  If  air  is  left  in  the  tubes,  cannula  or  vein,  then  the 
animal  may  die  of  air  embolism  when  the  drug  is  injected. 
Ahvays  carry  out  this  teclmic  ivlien  putting  an  injecting 
cannula  into  a  vein. 

To  dissect  out  the  right  femoral  vein  consult  Fig.  199. 
Place  the  tip  of  the  finger  in  the  inguinal  region  just  at 
the  lower  outer  edge  of  the  abdomen.  The  pulsations  of 
the  femoral  artery  will  be  felt  just  beneath  the  skin.  With 
the  large  forceps  pick  up  a  narrow  fold  of  the  skin  directly 
over  the  pulsations  and  cut  this  fold  away  ivit'li  the  scissors 
as  shown  in  the  illustration.  Do  not  use  a  scalpel.  When 
the  skin  and  fascia  are  thus  cut  away  an  opening  resem- 
bling that  shown  in  Fig.  95  will  be  made.  With  a  blunt- 
pointed  probe  dissect  away  the  fascia  between  the  sartorius 
and  adductor  muscles.  The  vessels  will  be  seen  in  the 
floor  of  this  triangular  space  as  shown  in  Fig.  96.  Use 
only  the  prohe  or  hlunt-pointed  forceps  for  the  dissection. 
When  about  one-half  inch  of  the  vein  has  been  freed  from 
the  fascia  slip  an  aneurism  needle  under  the  vessel  and  lift 


PRELIMINARY    OPERATIONS 


95 


it  up.  Free  it  from  fascia  for  a  distance  of  three-quarters 
or  one  inch  and  then  tuith  the  forceps  place  two  ligatures 
loosely  under  it.  Tie  these  loosely  and  place  a  bull-dog 
on  the  vessel  close  up  to  the  proximal  end  of  the  freed 
space.    The  distal  ligature  is  now  .tied  tightly,  the  vessel  is 


Cephalad 


Fig.    95. — A   blunt  probe   is   used  to   dissect   the   fascia   away   from   the   femoral   artery   and 

vein. 

lifted  on  the  aneurism  needle,  and  with  the  scissors  a  cut 
about  three-fourths  across  the  vessel  is  made  close  to  the 
distal  tied  ligature.  If  the  segment  of  the  vessel  was  full 
of  blood  the  assistant  should  hold  a  piece  of  cotton  over 


Cephalad 


Fig.    96. — Position   and   relations   of   the  vein,    artery   and  nerve. 

the  points  of  the  scissors  as  the  cut  is  made.  The  opera- 
tor now  holds  the  vessel  open  {supporting  it  on  the  hook 
of  the  aneurism  needle)  with  the  large  sharp-pointed  for- 
ceps while  the  assistant  inserts  the  cannula,  running  out  a 


96  EXPERIMENTAL   PHARMACOLOGY 

little  salt  solution  at  the  same  time.  The  camiula  is  now 
tied  in  and  the  remaining  salt  solution  is  run  out  through 
the  side  tube.  The  relations  of  the  vein,  artery,  and  nerve 
are  shown  in  Fig.  96.  You  ivill  need  to  Txfiow  these  rela- 
tions ivell  for  future  operations. 

Now  pour  into  the  empty  burette  about  fifteen  cubic  cen- 
timeters of  adrenaline  solution  1-10,000  (Parke,  Davis  and 
Co.,  adrenaline  chloride;  or  synthetic  levorotatory  adren- 
aline, Farbwerke-Hoechst  Company,  New  York.  The  former 
is  advisable).  Wash  out  a  little  of  the  solution  to  get  all 
air  out  of  the  tubes.  Save  the  solution  washed  out  and 
return  it  to  the  burette. 

(d)  Recording  Blood-pressure. — Bring  the  writing  point 
of  the  manometer  (mercury)  to  the  smoked  surface  of  the 
drum.  It  is  exceedingly  desirable  for  the  manometer  to 
carry  a  signal  magnet  which  marks  the  base  line,  or  line 
of  zero  pressure,  and  at  the  same  time  marks  the  time 
intervals  as  recorded  from  a  master  clock,  Jaquet  chrono- 
graph, metronome,  or  other  time  recording  device.  The 
construction  of  the  manometer  is  shown  in  Fig.  6.  This 
illustration  also  shows  the  method  of  connecting  the  man- 
ometer to  the  pressure  bottle.  The  best  anti-coagulating  so- 
lution to  be  placed  in  the  pressure  bottle  for  filling  the  tubes, 
right  limb  of  the  manometer  and  the  cannula,  is  a  solution 
of  sodium  citrate  (5  to  10  per  cent).  (Several  other  salts, 
Na2S04,  NaHCOo,  MgS04,  etc.,  in  varying  strengths,  are 
sometimes  used.)  The  signal  magnet  point  should  mark 
about  three-fourths  of  an  inch  to  the  left  of  the  manometer 
pointer.  This  avoids  breaks  in  the  time  record  in  the 
early  part  of  the  tracings.  Hold  a  battery  jar  under  the 
wash-out  tube  and  open  the  corresponding  clip.  Now  open 
the  clip  at  the  top  of  the  manometer.  The  sodium  citrate 
solution  will  quickly  run  down  and  fill  the  tubes,  manometer, 
and  cannula.  All  air  will  be  washed  out.  Close  the  clip 
on  the  side  tube  while  the  upper  clip  remains  open.  In 
this  manner  run  in  citrate  solution  sufficient  to  raise  the 


PRELIMIISTARY    OPERATIONS  97 

pressure  in  the  manometer  until  the  manometer  pointer 
writes  about  one  and  one-half  inches  ahove  the  base  line. 
Do  not  raise  this  iwessure  too  high.  Why?  See  that  both 
clips  are  tightly  closed  and  then  remove  the  bull-dog  from 
the  artery.  The  pressure  in  the  manometer  should  rise 
sufficiently  to  lift  the  writing  point  about  three-fourths  or 
one  inch  higher  than  it  was. 

The  pressure  bottle  should  be  suspended  from  a  pulley 
at  the  ceiling  and  the  bottle  should  be  kept  about  four  or 
five  feet  above  the  table.  Some  workers  put  the  pressure 
bottle  on  the  table  and  use  compressed  air  to  force  the 
fluid  out.  The  writer  advises  that  this  method  be  avoided 
at  least  in  student  work,  for  all  the  space  on  the  table  top 
is  needed  for  other  apparatus.  Furthermore,  it  sometimes 
happens  that  students  do  not  projDerly  close  the  clip  at  the 
top  of  the  manometer  and  then  the  dog  may  soon  bleed 
to  death  by  forcing  blood  out  into  the  tubes  and  pressure 
bottle,  Avhile  at  the  same  time  citrate  solution  rather  quickly 
passes  doA\m  into  the  carotid  artery.  This  solution  is  very 
poisonous  and  soon  kills  the  heart.  If  the  bottle  is  sus- 
pended above  the  table  the  instructor  can  quickly  see  if  any 
blood  is  backing  up  into  the  bottle.  In  addition  it  is  much 
easier  for  the  instructor  to  see  at  a  glance  just  how  much 
citrate  solution  each  group  of  students  has  ahead  for  the 
experiment. 

(e)  Recording  Respiration. — Xear  the  middle  of  the 
thorax  pass  the  long  string  of  the  stethograph  drum  under 
the  dog  (use  the  hook  of  an  aneurism  needle  to  reach  un- 
der the  animal)  and  bring  it  up  on  the  opposite  side.  Ad- 
just the  two  strings  of  the  stethograph  with  a  moderate 
tension  and  clamp  them  together  with  a  hemostat  or  bull- 
dog. If  too  little  movement  is  thus  secured  for  the  stetho- 
graph membranes  place  fairly  large  wads  of  cotton  under 
the  strings  on  either  side  of  the  chest.  Now  connect  a 
rubber  tube  (which  carries  near  the  middle  a  T-tube  with 


yy  EXPERIMENTAL   PHARMACOLOGY 

a  side  tube  and  clip)  to  the  stethograph  drum  and  attach 
the  other  end  of  the  tube  to  a  tambour  which  writes  on 
the  drum.  The  respiratory  record  should  be  adjusted  to 
give  an  amplitude  of  about  one  inch  and  should  be  re- 
corded heloiv  the  hlood-pressure  and  about  one-half  inch 
above  the  base  line  (recorded  by  the  time  signal  magnet 
on  the  manometer  or  by  a  signal  magnet  placed  separately 
on  a  stand). 

(f)  Adjustment  of  Writing  Points. — On  the  drum  now 
adjust  the  writing  point  of  the  manometer  in  such  a  posi- 
tion that  if  the  blood-pressure  falls  very  low  then  the  writ- 
ing point  will  just  barely  pass  do\\Ti  to  the  right  of  the  re- 
spiratory tambour.  This  is  an  important  point  in  technic 
and  must  ahvays  be  foreseen  and  provided  for  especially 
if  three  or  four  tracings  are  being  recorded  at  the  same 
time.  The  anesthetist  should  have  maintained  an  even 
anesthesia  throughout  these  procedures.  His  guide  is  the 
depth  and  regularity  of  the  respiration.  After  the  blood- 
pressure  record  is  started  then  it  also  furnishes  valuable 
information  regarding  the  depth  of  the  anesthesia.  The 
respiration,  hoAvever,  is  the  most  important  and  should  be 
watched  closest.  While  the  anesthetist  is  personally  re- 
sponsible for  the  life  of  the  animal  yet  it  is  the  duty  of 
each  student  in  the  group  to  keep  as  careful  and  constant 
a  watch  on  the  animal  as  possible.  Each  animal  lost  care- 
lessly should  be  carefully  checked  up  against  the  anes- 
thetist and  his  group,  and  should  be  duly  considered  in 
making  out  the  respective  grades  at  the  end  of  the  course. 

There  are  certain  objections  to  this  method  of  record- 
ing the  respiration,  but  it  is  probably  the  best  one  for 
student  use, 

(g)  Other  Methods  of  Recording  Respiration. — Some 
workers  record  respiration  by  connecting  the  tambour  to 
the  side  tube  of  the  tracheal  cannula.  If  ether  is  given 
through  a  bottle  or  if  artificial  respiration  is   suddenly 


PRELIMIIsrAllY    OPERATIONS  99 

needed  this  method  is  of  but  little  use.  If  the  animal  be 
kept  under  the  influence  of  a  hypnotic  such  as  chloretone, 
then  it  may  be  of  some  use.  It  is  best,  however,  that  the 
method  be  avoided,  at  least  by  students.  Cushny  has  de- 
vised a  special  apparatus  for  recording  respiration  where 
greater  accuracy  is  required.  The  apparatus  consists  of 
a  long  narrow  box  with  one-half  or  more  of  the  ends  (up- 
per part)  removed.  The  box  can  be  turned  bottom  up- 
wards over  the  animal  as  it  lies  on  the  operating  table.  A 
very  thin  flexible  rubber  membrane  is  stretched  loosely  in- 
side the  box,  being  attached  (air  tight)  to  the  sides  and  ends. 
The  bottom  of  the  box  (now  turned  upward)  thus  forms  a 
closed  cavity  over  the  entire  chest  and  abdomen  of  the 
animal  (rabbit).  When  the  animal  inspires  the  rubber 
membrane  mil  be  lifted  up  and  the  air  in  the  ux)per 
part  of  the  box  will  be  driven  out  through  a  tube  to  the 
recording  tambour.  Another  tube  in  the  box  carries  a 
short  rubber  tube  and  a  screw  clamp.  This  serves  as  an 
adjustable  by-pass  for  the  excess  air  if  the  tambour  is  too 
small  to  record  all  changes  (as  are  all  tambours  now  on 
the  market).  A  small  spirometer  may  also  be  used  to  re- 
cord the  respiratory  movement  by  this  method.  (See  also 
Cushny  and  Lieb,  Journal  of  Pharmacology  and  Experi- 
mental Therapeutics,  1915,  vi,  451.) 

Another  method  of  recording  respiration  consists  in  at- 
taching a  string  to  the  tip  of  the  ensiform  (Xiphoid)  car- 
tilage by  means  of  a  pin  hook.  The  string  passes  over 
pulleys  to  a  lever  (or  to  two  connected  tambours)  Avhich 
writes  on  the  drum. 

(h)  Beginning  of  the  Records. — Take  the  bull-dog  off 
the  carotid  artery  if  this  has  not  been  done  before  and  ob- 
serve the  blood-pressure  tracing  on  the  drum.  Adjust  the 
pointer  and  also  the  respiratory  tambour  if  it  is  not  al- 
ready making  a  satisfactory  record.  Bo  not  proceed  ivitli 
the  experiment  until  a  perfectly  satisfactory  record  is  he- 


100  EXPERIMENTAL   PHARMACOLOGY 

ing  obtained.    Be  sure  the  drum  is  wound  up  and  set  for 
a  slow  speed. 

Start  the  drum  and  take  two  inches  of  normal  record, 

2.  Stimulate  the  right  vagus  nerve  (the  drum  is  kept 
going)  witla  a  moderately  strong  tetanizing  current.  What 
are  the  effects  on  blood-pressure  and  respiration?  How 
do  you  explam  this! 

3.  Open  the  left  eye  and  while  observing  the  pupil  closely 
stimulate  the  left  vagus  nerve.  What  do  you  observe? 
How  do  you  explain  this!    Repeat  this  on  the  right  side. 

4.  Crowd  on  the  ether  vapor  by  shutting  off  the  straight 
end  (for  air)  of  the  tracheal  cannula  and  shaking  up  the 
ether  in  the  bottle.  The  dog  thus  breathes  a  very  concen- 
trated vapor.  What  effect  has  this  on  the  respiration  and 
blood-pressure!  Do  the  heart  beats  become  slower!  Can 
you  determine  this  mth  a  mercury  manometer!  Increase 
in  the  amplitude  (up  and  doA\m)  of  the  manometer  strokes 
indicates  a  slowing  of  the  heart.  ^Vhy!  A^Hiat  mechanical 
factors  are  involved!  Do  not  mistake  the  reflected  effects 
of  respiration  on  the  blood-pressure  for  a  change  in  the 
amplitude  of  each  separate  heart  beat.  AIIoav  the  animal 
to  return  to  normal.  Stimulate  the  vagi  nerves.  Are  the)^ 
more  or  less  active  in  affecting  the  heart  and  respiration 
than  before!  What  nerves  are  concerned  in  these  respira- 
tory effects  and  over  Avhat  paths  do  the  impulses  travel! 
At  what  points  might  an  excess  of  ether  affect  these! 

5.  Give  the  animal  a  few  breaths  of  chloroform  vapor. 
This  is  best  done  by  taking  an  empty  ether  bottle  (1  pint 
milk  bottle)  and  putting  about  two  cubic  centimeters  of 
chloroform  into  it  (Fig.  89).  The  cork  of  the  ether  bot- 
tle connected  to  the  dog  is  now  removed  and  inserted  into 
the  second  bottle.  The  chloroform  vapor  mil  be  quickly 
inhaled  by  the  animal  and  there  will  be  an  immediate  change 
in  the  blood-pressure  and  respiration.  Do  not  alloiv  these 
changes  to  go  too  far.  Remove  the  chloroform  bottle  and 
allow  the  dog  to  recover.    Replace  the  ether.    This  may  be 


ASPHYXIA    AND    RESUSCITATION  101 

repeated  two  or  three  times  to  secure  more  sets  of  rec- 
ords. Now  inject  one-fourth  cubic  centimeter  of  adren- 
aline. Do  you  get  a  normal  effect!  Ask  the  instructor 
about  the  appearance  of  this  record.  You  may  need  a 
larger  dose.  Compare  the  effects  of  ether  with  those  of 
chloroform  on  the  blood-pressure  and  respiration.  Which 
do  you  consider  safer?    Why? 

6.  Allow  the  animal  to  recover.  Then  place  some  ethyl 
bromide  (3  or  4  c.c.)  in  a  second  milk  bottle  and  attach  it 
to  the  tracheal  cannula.  Compare  the  action  of  this  drug 
with  that  of  ether  and  chloroform.  Learn  the  odor  of 
each  of  these  drugs. 

7.  If  Harvard  kymographs  are  being  used  one  student 
should  see  to  it  that  at  least  one  well  smoked  extra  drum 
is  always  available.  Allow  the  animal  to  return  to  a  satis- 
factory^ condition  and  then  close  off  both  openings  from 
the  tracheal  cannula.  The  animal  will  soon  become  as- 
phyxiated. Be  sure  you  secure  a  good  tracing  of  this. 
Observe  carefully  the  changes  in  blood-pressure  and  res- 
piration. How  do  you  explain  these?  How  do  the 
respiratory  movements  affect  the  blood-pressure?  Con- 
tinue the  asphyxia  until  either  the  heart  or  the  respiration 
finally  stops.  What  is  the  immediate  cause  of  death?  Now 
open  the  tracheal  cannula  and  at  once  give  the  animal 
artificial  respiration  (the  ether  should  be  removed)  either 
with  a  hand  bellows,  or  better,  by  means  of  a  special 
respiration  machine  (Fig.  360).  Inject  one  cubic  centi- 
meter of  adrenaline  solution.  The  lungs  should  be  inflated 
about  twent}^  or  twenty-five  times  per  minute.  Does  this 
affect  the  heart  or  respiratory  center?  Continue  it  for 
ten  minutes  if  the  animal  does  not  recover  sooner.  Stop 
when  you  detect  sufficient  signs  of  recover}^  and  alloAV  the 
animal  to  return  to  normal.  Now  give  the  animal  suffi- 
cient chloroform  to  stop  both  heart  and  respiration.  Im- 
mediately apply  artificial  respiration  and  try  to  revive  the 
dog  as  you  did  before.    Compress  the  chest  over  the  heart 


102  EXPERIMENTAL   PHARMACOLOGY 

intermittently  with  both  hands.  Watch  the  movements  of 
the  manometer  as  you  compress  the  heart.  Does  this  af- 
fect the  blood-pressure?  Quickly  inject  from  the  burette 
two  cubic  centimeters  of  adrenaline  solution  and  continue 
the  artificial  respiration  and  heart  massage  for  ten  min- 
utes if  the  animal  does  not  recover  sooner.  What  treat- 
ment would  you  advise  for  threatened  death  under  an 
anesthetic  ?  How  would  you  apply  this  treatment  in  a  mod- 
ern hospital?  If  the  animal  revives  (it  of  course  never 
comes  out  from  under  the  influence  of  the  anesthetic)  then 
again  clamp  off  the  A^dnd  pipe  and  allow  it  to  die  of  as- 
phyxia. 

8.  If  time  permits  make  the  following  dissections :  Open 
the  chest  by  a  median  incision  over  the  sternum.  To  do 
this  incise  the  skin  and  fascia  down  to  the  sternum,  and 
saw  (Fig.  104)  this  through  exactly  in  the  median  line. 
(See  Fig.  105.)  Pull  open  the  chest  from  side  to  side  and 
expose  the  lungs  and  heart  (inside  the  pericardium).  In- 
flate the  lungs.  Open  the  pericardium  and  expose  the 
heart.  Observe  all  the  important  structures  in  the  chest. 
Cut  the  phrenic  nerves  where  they  lie  on  the  pericardium. 
Could  you  make  this  dissection  in  a  living  animal? 

9.  Carefully  clean  up  the  table,  manometer  tubing,  can- 
nulas, etc.,  and  put  away  all  your  apparatus.  It  is  im~ 
perative  for  each  group  to  clean  up  its  own  apparatus  after 
each  experiment.  The  animal  must  be  put  in  a  garbage 
can  or  box  with  the  others  and  should  be  burned  in  the 
furnace  at  the  power  or  heating  plant. 

The  records  obtained  during  the  experiment  should  be 
labeled  at  once.  The  appearance  of  the  record  can  often  be 
greatly  improved  by  drawing  a  few  straight  lines  horizon- 
tally through  the  tracings  by  rotating  the  drum  against  a 
stationary  tambour  pointer  before  the  paper  is  removed 
from  the  drum.  (See  Fig.  190.)  Rough  notes  should  be 
made  during  the  experiment.  The  record  is  varnished  and 
dried,  and  the  permanent  notes  should  be  written  up  as  soon 
as  possible. 


ETHEK^   CHLOROFORM,   ETHYL  BROMIDE 


103 


EXPERIMENT  V. 

Ether,  Chloroform,  Ethyl  Bromide.     (Dog:  Motor  Areas, 
Blood-Pressure,  Blood,  Heart.) 

1.  Arrange  a  dog  as  in  Experiment  IV,  for  recording 
blood-pressure.  Put  adrenaline  solution  in  the  injecting 
burette  (in  the  femoral  vein).  Be  sure  the  anesthesia  is 
regular  and  sufficiently  deep. 

2.  Loosen  the  dog's  mouth  and  the  right  fore  leg.  Turn 
the  head  and  part  of  the  chest  over  toward  the  left  so  as 
to  leave  the  top  of  the  head  turned  well  over  to  the  right. 
If  the  instructor  advises  it  turn  the  dog's  head  entirely 


Fig.   9T . — Removal   of   a  triangular  area  of  skin  and  fascia   over   the   skull   for   a  trephine 

opening. 

over  so  that  the  top  of  the  skull  is  directed  upward.  In 
this  case  watch  that  the  respiration  is  not  hampered  or 
that  the  carotid  or  tracheal  cannulas  do  not  become  dis- 
turbed by  compression  of  the  carotid  artery  or  trachea. 
Observe  Fig.  97  carefully.  Make  a  median  longitudinal 
incision  in  the  skin  and  fascia  down  to  the  skull  as  sho^^m 
in  the  illustration.  With  large  scissors  (Fig.  98)  cut  out 
a  triangular  piece  of  skin  and  fascia.    At  the  place  marked 


104 


EXPERIMENTAL   PHARMACOLOGY 


'^C'^  in  Fig.  99  a  curved,  line  will  mark  the  point  of  at- 
tachment of  the  temporal  muscle  [T).  With  a  scalpel  cut 
the  edge  of  the  muscle  loose  from  the  bone  exactly  in  this 
line.    Now  dissect  the  muscle  loose  from  the  skull  by  cut- 


Fig.   98. — Six   inch  tinner's   snips   used   for   cutting  thick  skin   and   fascia,   etc. 

ting  the  periosteum  from  the  bone  and  reflecting  the  muscle 
outward  from  the  median  line.  Be  sure  to  keep  the  dis- 
section and  cutting  close  cIoaati  to  the  bone  to  avoid  the 


Fig.  99. — A  trephine  opening  (O)  has  been  made  in  the  skull  {S)  and  the  dura 
mater  (B)  beneath  is  exposed.  The  electrodes  can  be  applied  to  the  dura  mater  over 
the  various  centers  in  the  motor  area.  C,  line  of  attachment  of  the  reflected  temporal 
muscle   {T).     M,  median  line  beneath  which  is  the   great   longitudinal  sinus. 

muscular  blood  vessels.  Pull  the  reflected  edge  of  the 
muscle  upward  with  a  hemostat  as  shown  in  Fig.  99.  Now 
take  a  trephine  instrument  (Fig.  100)  and  at  a  point  about 


EXPOSURE   or    MOTOR  AREAS 


105 


one-half  or  three-fourths  inch  from  the  median  ]ine  make 
an  opening  through  the  skull.  (It  may  be  necessary  later 
to  enlarge  this  opening.)  Be  sure  to  keep  far  enough  out 
from  the  median  line  to  avoid  the  great  longitudinal  sinus 
inside  the  skull  (S).    (If  this  is  opened  accidentally  quickly 


100. — Trephine. 


remove  the  trephine  instrument  and  tightly  plug  the  open- 
ing with  cotton  to  stop  the  hemorrhage.  Then  turn  the 
animal  over  and  perform  the  operation  on  the  left  side.) 
Remove  the  button  of  bone  and  the  dura  mater  over  the 


106 


EXPERIMEIsTTAL   PHARMACOLOGY 


brain  should  be  seen  as  shown  in  Fig.  99.  Now  allow  the 
anesthesia  to  become  as  light  as  possible  without  letting 
the  animal  come  out  from  under  the  influence  of  the  ether 
too  much.  With  the  platinum  electrodes  (medium  tetaniz- 
ing  current)  begin  to  stimulate  the  exposed  dura  mater  at 
various  points.  Try  to  pick  out  some  centers  for  various 
muscular  movements.     Observe  Fig.   101.     Make  careful 


LoiKjifudinsI  sulcus 

CrucidI  sulcus  {Fissure  of 'Rolando) 

Center  for  Ihe  neck  muscles. 

penter  jvr  I'he  exi-ensorj  s- 
adduciorjf  of  fhe  forelimo. 

center  for  ihe  flexors  s>- 
roiation  of  f/ie  forelimh. 

-cenier  for  i'he  nind  limb. 

ceni-er  for  ike  muscles 
innerval-ed  by  Me  facial. 


Fig.    101. — Upper    surface    of   a    dog's   brain.       (Modified    from    Sisson.) 

note  of  the  position  of  the  electrodes  for  each  of  these 
centers  and  observe  closely  the  extent  and  strength  of  the 
movements  produced.  Be  sure  you  understand  the  an- 
atomy of  the  nervous  paths  by  which  these  movements  are 
originated  and  controlled.  Now  deepen  the  anesthesia  and 
again  stimulate.     Is  there  any  change  in  the  response  of 


ETHER,    CHLOROFORM,  ETHYL   BROMIDE 


107 


Again 


lighten  the  anesthesia  and   secure 


the  muscles? 

more  ''normal"  movements.  Now  give  the  animal  a  lit- 
the  {not  too  much)  chloroform  and  again  stimulate.  Are 
the  movements  affected  in  any  way?  How  does  this  com- 
pare with  ether!  If  the  instructor  advises  it  the  action  of 
ethyl  bromide  on  the  motor  areas  may  be  tried  also.  Re- 
place the  animal  in  the  usual  position  and  re-adjust  your 
apparatus. 


I 


Fig.    102. — "Straight"    glass   cannula.      Several    different   sizes    of    these    are    often    needed. 

3.  Dissect  out  one  femoral  artery  (Fig.  96)  and  place 
in  it  (pointing  toward  the  heart)  a  small  straight  cannula 
(Fig.  102).  Leave  a  bull-dog  clamp  on  the  artery  proxi- 
mal to  the  cannula.  Into  a  test  tube  draw  off  about  three 
or  four  cubic  centimeters  of  blood  from  the  artery,  and 
at  once  pour  an  equal  quantity  of  ether  into  the  blood. 
Shake  the  two  together  for  a  few  seconds  and  set  the  tube 


Fig.    103. — Hand  bellows. 

aside  for  two  or  three  minutes.  Then  observe  the  appear- 
ance of  the  blood.  Can  you  detect  any  changes'?  How  do 
you  exx)lain  this? 

4.  Repeat  this  with  chloroform.    Do  these  tubes  of  blood 
clot? 

5.  Repeat  with  ethyl  bromide. 

6.  Cardiometer. — Arrange  for  artificial  respiration.    If 


103 


EXPEKIMENTAL   PHARMACOLOGY 


possible  this  should  be  done  with  a  thoroughly  reliable  res- 
piration machine  (Fig.  360).  If  this  is  not  available  then 
use  a  hand  bellows  (Fig.  103).  Prepare  a  needle  and  thread 
and  four  strong  twine  (heav}^)  strings  about  eighteen 
inches  long. 

With  the  scalpel  make  a  median  longitudinal  incision  in 
the  skin  and  fascia  over  the  sternum.  The  incision  extends 
from  the  root  of  the  neck  to  the  end  of  the  xiphoid  cartilage. 
When  the  fascia  and  muscular  layers  come  into  sight  a 
number  of  blood  vessels  will  be  seen  passing  mesially  in 
pairs  to  the  midline  of  the  sternum  where  they  pass  into 
the  chest.    Do  not  cut  these  vessels  if  it  can  he  avoided 


Fig.    104. — Bandage   :aw. 


(which  is  sometimes  impossible).  In  the  center  line  it  is 
usually  possible  to  cut  between  the  ends  of  each  pair  of 
vessels  and  thus  avoid  much  hemorrhage. 

If  a  vessel  is  cut  clamp  it  with  a  hemostat.  The  bleed- 
ing should  soon  cease.  Have  plenty  of  absorbent  cotton 
(in  small  wads)  at  hand  to  sponge  off  the  operative  field. 
When  the  center  line  of  the  sternum  is  reached  then  take 
a  saw  (Fig.  104)  and  saw  open  the  chest  as  shown  in  Fig. 
105.  Start  the  artificial  respiration  as  soon  as  any  open- 
ing is  made  into  the  chest.  It  is  exceedingly  important  to 
keep  the  incision  in  the  center  line.    If  this  is  done  prac- 


OPENIlSrG  TPIE  CHEST 


109 


tically  all  important  blood  vessels  will  be  avoided.  Just 
inside  the  chest  the  mammary  vessels  will  be  fonnd  on 
each  side  of  the  midline.  These  vessels  shonld  be  sepa- 
rated, each  pair  remaining  attached  to  the  under  surface 
of  its  corresponding  side  of  the  sternum.  If  one  of  these 
vessels  is  cut  it  must  be  quickly  caught  with  a  hemostat 
and  then  a  string  is  pushed  (with  the  large  sharp-pointed 
forceps)  through  the  chest  wall  close  to  the  lateral  sternal 


Fig.    105. — Method   of   opening   the   chest   by   a   median    incision. 

border  and  the  end  brought  around  inside  the  chest.  This 
string  is  now  tied  firmly  and  should  shut  off  the  vessel  on 
one  side  of  the  cut  place.  But  a  second  string  is  generally 
needed  on  the  opposite  side  of  the  opening  in  the  vessel 
to  prevent  hemorrhage  from  the  other  end  of  the  vessel. 
All  hemorrhage  shoidd  he  checked  before  one  proceeds 
with  the  experiment.  'When  all  bleeding  has  stopped  then 
(with  the  forceps)  pass  the  four  large  twine  strings  through 


110  EXPERIMENTAL   PHARMACOLOGY 

tlie  margins  of  tlie  chest  Avails  as  shown  in  Fig.  106.  Tie 
these  ends,  draw  the  chest  wall  open,  and  fasten  the  strings 
to  the  operating  board  as  shown  in  Fig.  107. 

This  fully  exposes  the  lungs  and  the  heart  which  is  cov- 
ered by  the  pericardial  sac.  Did  you  see  the  anterior 
mediastinum!  What  became  of  it!  With  scissors  open 
the  pericardium  in  the  midline.  Then  bring  the  cut  edges 
of  the  pericardium  out  laterally  and  sew  them  (with  two 
or  three  stitches  on  each  side)  to  the  chest  wall.  This 
forms  a  kind  of  hammock  in  Avhich  the  heart  lies.  The 
animal  must  be  given  sufficient  ether  to  keep  it  quiet  all 
the  time.  Observe  carefully  the  beating  of  the  heart  and 
the  movements  of  the  lungs.  Did  the  blood-pressure  fall 
much  when  you  opened  the  chest?  It  should  not.  Does 
the  heart  rise  and  fall  as  the  lungs  are  inflated  and  de- 
flated? If  so,  try  to  reduce  the  extent  of  inflation  a  little 
and  see  if  the  animal  does  well  (blood-pressure  remains 
normal  and  convulsive  movements  do  not  appear).  This 
rise  and  fall  of  the  heart  is  the  most  troublesome  thing 
concerned  in  the  taking  of  heart  tracings.  Now  take  the 
cardiometer  (Fig.  108)  and  stretch  the  rubber  membrane 
outward  from  the  opening,  rolling  part  of  the  edge  of  the 
membrane  back  over  the  metal  rim.  Now  place  the  cardi- 
ometer down  over  the  heart  (ventricles  only,  see  Fig.  107) 
and  bring  the  membrane  down  to  the  auriculo-ventricular 
groove.  Roll  the  edge  of  the  membrane  off  the  metal  part 
and  allow  the  opening  in  the  membrane  to  close  around  the 
auriculo-ventricular  groove.  Does  the  blood-pressure  re- 
main normal?  If  not,  wait  a  little  and  if  necessary  re- 
adjust the  cardiometer.  Connect  the  cardiometer  tube  with 
a  recording  tambour  which  may  write  either  above  or  be- 
low the  blood-pressure,  depending  on  whether  the  pressure 
is  low  or  high  respectively.  Adjust  all  writing  points  and 
take  two  or  three  inches  of  ''normal"  tracing.  The  cardi- 
ometer record  should  be  one  or  two  inches  in  amplitude. 


Fig. 


106. — Method  of  exposing  the  left   pulmonary  artery   and  vein.      /,,    linig.      P.  phrenic   nerve 
lying  on  the  pericardium   (H)    over  the  heart.     D,  the  diaphragm. 


CARDIOMETER  TRACINGS 


111 


Stiniulate  one  vagus  nerve  and  see  how  this  affects  the 
tracings.  Allow  the  heart  to  recover  and  take  two  inches 
more  of  "normal"  tracing.  Now  crowd  on  the  ether  and 
note  the  effect  on  the  pressure  and  cardiometer  tracings. 
What  does  the  cardiometer  tracing  show  with  respect  to 
the  heart?  Be  sure  you  describe  this  fully  and  correctly 
in  your  notes. 


Fig.  107. — Method  of  applying  the  cardiometer  over  the  ventricles.  Artificial  respi- 
ration is  carried  on  either  with  a  hand  bellows  or  by  an  artificial  respiration  machine. 
Tiie  ether  bottle  has  a  by-pass  so  the  amount  of  anesthetic  can  be  regulated.  The  excess 
air  escapes  through  the  tube  in  the  straight  end  of  the  tracheal  cannula  which  is  regu- 
lated by  the  screw  clamp  to  give  the  desired  amount  of  expansion  and  exhaustion  of  the 
lungs. 

Allow  the  animal  to  recover  and  then  give  it  some  chloro- 
form. How  does  this  compare  with  ether?  Now  inject 
one-half  cubic  centimeter  of  adrenaline.  How  does  this 
affect  the  heart?  Is  the  drum  going  fast  enough  to  show 
the  indiAddual  heart  beats? 

Allow  the  animal  to  return  to  normal  and  then  give  it 


112 


EXPERIMENTAL   PHARMACOLOGY 


some  ethyl  bromide.    How  does  this  affect  the  heart?    In- 
ject a  little  adrenaline  and  let  the  animal  recover. 

(It  will  be  interesting  to  try  ethyl  chloride  also.  It  can 
be  sprayed  into  one  of  the  rubber  tubes  going  to  the  tracheal 
cannula.  To  do  this  an  extra  T-tube  may  be  placed  in  the 
circuit.) 


Fig.    108. — Cardiometer.       (See    also    Fig.    143.) 


7.  Dissection  of  Pulmonary  Artery  and  Vein. — Remove 
the  cardiometer  and  cut  the  stitches  that  hold  the  peri- 
cardium to  the  chest  wall.  Pull  the  pericardium  and  heart 
all  over  toward  the  right  side  of  the  animal.  Observe  the 
left  pulmonary  veins  at  the  root  of  the  lung.  Observe  Fig. 
106  closely.  At  the  base  of  the  heart  observe  the  aorta 
passing  back  posteriorly  and  then  turning  caudalward.  In 
the  hollow  of  the  arch  of  the  aorta  between  it  and  the 
heart  a  curved  eminence  covered  with  white  fascia  will  be 
seen  coming  from  the  base  of  the  heart  and  passing  down- 
w^ards,  outwards  and  backwards  into  the  lung  beneath  the 
most  prominent  pulmonary  vein.  With  a  blunt  probe  care- 
fully dissect  away  some  of  the  fascia  over  the  curved  emi- 


NITROUS    OXIDE^    CARBON    DIOXIDE,    OXYGEN  113 

nence,  and  the  left  pulmonary  artery  can  be  seen  passing 
out  into  the  base  of  the  lung.  Place  an  aneurism  needle 
beneath  the  artery,  raise  it  up  and  clear  a  section  of  the 
artery  about  three-fourths  of  an  inch  long  with  the  probe. 
Could  you  put  a  cannula  into  this  artery  and  record  the 
pulmonary  blood-pressure?  The  heart  will  probably  have 
ceased  beating  by  this  time.  If  it  has  not,  stop  the  respira- 
tion and  let  the  animal  die.  If  time  'permits  it  ivill  he  very 
instructive  to  try  to  revive  the  heart  hy  massage  and  by 
injecting  adrenaline.  Keep  up  the  artificial  respiration 
during  these  efforts. 


EXPERIMENT  VI. 

Nitrous  Oxide,  Carbon  Dioxide,  Oxygen.     (Frog:  Central 
Nervous  System.) 

1.  Place  a  frog  in  a  one  pint  milk  bottle  as  shown  in  Fig. 
109.  Arrange  a  nitrous  oxide  tank  (and  an  oxygen  tank 
also  if  the  laboratory  can  afford  one — if  not  omit  the  oxy- 
gen) as  shown  in  the  illustration.  The  apparatus  shown 
in  Fig.  110  may  also  be  used  if  a  nitrous  oxide  tank  is  not 
available.  Observe  (and  count)  the  rate  of  the  frog's  res- 
piration, lymph  heart  beats  and  heart  beats.  Note  the 
size  of  the  pupils,  position  which  the  frog  assumes,  etc. 
Now  open  the  N2O  tank  a  little  and  run  into  the  bottle  a 
very  small  amount  of  the  gas.  Make  a  note  of  the  time 
of  day.  The  outlet  must  he  opened  as  the  gas  is  run  in, 
for  these  tanks  may  have  1000  pounds  or  more  pressure 
to  the  square  inch  and  Avould  quickly  burst  the  bottle  or 
blow  out  the  cork.  Watch  the  frog  carefully  as  it  begins 
to  breathe  the  gas.  Does  it  show  any  signs  of  suffocation? 
There  Avas  already  sufficient  oxygen  in  the  bottle  to  run 
the  frog  some  time.  Gradually  run  in  more  NoO  and  watch 
carefully  for  the  first  symiDtoms  sIioaati  by  the  frog.  As 
the  atmosphere  in  the  bottle  becomes  more  and  more  filled 


114 


EXPEKIMENTAL   PHAEMACOLOGY 


with  the  gas  the  frog  will  manifest  distinct  s^Tuptoms. 
How  long  does  it  take  to  completely  anesthetize  the  ani- 
mal? When  this  stage  is  reached  count  the  respirations, 
lymph  heart  beats  and  heart  beats.  Inject  a  little  oxygen 
from  time  to  ^ime  and  see  if  the  animal  comes  ont  from 


Wheel  wrench 
\ 


Fig.   109. — Administration  of  nitrous  oxide   or  oxygen  to  a  frog. 

under  the  anesthetic.  As  the  oxygen  increases  in  the 
bottle  the  frog  will  recover.  How  long  does  this  take  and 
how  long  a  time  is  required  to  anesthetize  the  frog  in  the 
first  place?  How  does  this  anesthetic  compare  with  ether 
or  chloroform  or  ethyl  bromide? 

2.  Place  another  frog  in  the  bottle.     Note  the  time  of 


l^ITROUS  OXIDE  ANESTHESIA 


115 


day.  Turn  on  the  N2O  and  fill  the  bottle  at  once  with  this 
gas  (washing  most  of  the  air  out  of  the  bottle  with  the 
N2O).  How  long  does  it  take  to  anesthetize  the  frog?  When 


Fig.  110. — Method  for  making,  purifying  and  administering  nitrous  oxide  to  a  frog. 
Strong  solutions  of  ferrous  sulphate,  sodium  hydrate  and  concentrated  sulphuric  acid 
are  placed  in  the  wash  bottles. 


Fig.  111. — Yoke  for  tanks  of  oxygen,  nitrous  oxide  or  carbon  dioxide.  These  yokes 
are  attached  to  the  tanks  and  a  rubber  tube  is  slipped  over  the  nozzle  of  the  yoke. 
When  the  valve  of  the  tank  is  opened  a  little  the  oxygen  passes  out  through  the  tube. 
The  yokes  can  be  obtained  of  dealers  in  surgical  supplies  or  from  the  I^ennox  Chemical 
Company,  Cleveland,  Ohio   (Price  $  .75). 


the  animal  is  deeply  anesthetized  remove  it  quickly  from 
the  bottle  and  see  how  long  it  takes  for  complete  recovery. 


116 


EXPERIMENTAL   PHARMACOLOGY 


Keep  a  record  of  these  periods  of  time.     Does  the  frog 
again  become  completely  normal? 
3.  Place  another  frog  in  the  milk  bottle.    Now  inject  CO2 


Fig.    112. — A    double    yoke    for    holding    gas    tanks.      Made   by    bolting    together    two    bars 

of   iron. 


Fig.    113. — Yoke    for   holding   gas    tanks.      Made    of    gas    piping    and    fittings    (see    chapter 

on   shop   work). 

into  the  bottle.    This  may  be  done  from  a  tank  or  from  a 
Guthrie  generator  (Fig.  114).     Observe  the  effect  on  the 


IS^ITROUS  OXIDE^  ETHYL  CHLORIDE^  CARBON  DIOXIDE         117 

animal.  How  is  the  respiration  affected?  How  does  this 
compare  with  the  action  of  N2O  ?  If  you  have  oxygen,  run 
some  of  this  into  the  bottle  and  see  if  this  counteracts  the 
COo. 


Fig.    114. — Guthrie's   carbon   dioxide   generator.      Two   quart   milk  bottles  are   used  to   hold 
blocks  of  marble  and  dilute   acid    {A)    and   the   wash  water    (bottle  B). 


EXPEEIMENT  VII. 


Nitrous  Oxide,  Ethyl  Chloride,  Carbon  Dioxide,  Increased 
Atmospheric  Pressure,  (Decreased  Atmospheric  Pres- 
sure).    (Frog,  Guinea  Pig,  Rat,  Kitten,  or  Pup.) 

1.  Place  a  frog  and  a  guinea  pig  (or  other  small  mam- 
mal— see  that  the  frog  is  protected)  in  a  large  bottle  ar- 
ranged as  illustrated  in  Fig.  115.    Open  the  outlet  and  run 


118 


EXPERIMEliTTAL   PHARMACOLOGY 


some  oxygen  into  the  bottle.  What  effect  does  this  have  on 
the  animals  ?  It  is  to  be  noted  that  this  experiment  permits 
comparison  of  the  relative  effects  of  the  substances  ad- 
ministered on  warm-blooded  and  cold-blooded  animals.  The 


OuHeir 
Cebauer!s  eihyl  chlorid 


Vie  115.— Method  for  studying  the  action  of  nitrous  oxide,  ethyl  chloride,  carbon 
dioxide,  oxygen,  increased  (or  decreased)  atmo'spheric  pressure  on  warm  and  cold-blooaea 
animals. 

skin  absorption  or  excretion  of  the  frog  should  be  held  in 
mind.  Increase  the  amount  of  oxygen  in  the  bottle.  Then 
with  the  greatest  caution  raise  the  oxygen  pressure  in  the 
bottle  by  closing  the  outlet  and  opening  the  clip  on  the  tube 


ATMOSPPIERIC  PRESSURE    CHAXGES  119 

going  to  the  manometer  while  more  oxygen  is  run  in.  Do 
not  blow  out  the  mercury  by  turning  on  the  oxygen  sud- 
denly. What  effect  has  this  increased  pressure  on  the  ani- 
mals 1 

2.  If  a  suction  pump  (or  negative  air  pressure)  is  avail- 
able this  may  now  be  used.  Open  the  outlet  and  connect 
this  to  the  suction  pump  or  negative  pressure  faucet.  Open 
the  clip  to  the  manometer  and  exhaust  the  air  in  the  bottle 
as  many  centimeters  of  mercury  as  the  oxygen  pressure  has 
been  raised.    What  effect  has  this  on  the  animals ! 

3.  Wait  a  few  minutes  to  note  how  the  animals  act  and 
then  again  open  the  outlet  and  equalize  the  pressure  inside 
and  outside  of  the  bottle.  Roll  up  four  or  five  sticks  of 
sodium  or  potassium  hydrate  in  wire  gauze  and  put  them 
in  the  bottle  in  such  a  position  that  the  aninials  cannot 
touch  the  alkali.  What  is  the  purpose  of  this?  Be  sure 
the  alkali  does  not  rest  directly  on  the  bottom  of  the  bot- 
tle. Why?  Allow  the  animals  to  become  quiet  again  and 
then  begin  to  gradually  run  N2O  into  the  bottle,  leaving  the 
outlet  open  as  gas  is  injected.  Bring  on  the  anesthesia  by 
very  gradual  degrees  and  do  not  excite  the  animal  if  pos- 
sible. Do  you  notice  any  symptoms  of  somnolence  in  either 
animal?  Or  do  you  note  s3^mptoms  of  excitement  and  con- 
vulsive jumping-like  movements?  After  the  animals  be- 
come completely  anesthetized  begin  to  admit  oxygen.  How 
long  does  it  take  to  produce  complete  anesthesia?  Be  care- 
ful that  the  oxygen  does  not  become  too  low.  If  this  occurs 
one  animal  may  die.  Which  one?  Is  it  possible  for  3^ou  to 
estimate  how  much  oxygen  (i.  e.,  what  per  cent)  you  admit 
by  closing  the  outlet  and  raising  the  atmospheric  pressure 
in  the  bottle  a  given  number  of  millimeters  of  mercury? 
Try  to  so  balance  the  proportions  of  N.O  and  oxygen  in  the 
bottle  that  you  can  maintain  a  regular  anesthesia  in  the 
animals  for  ten  or  fifteen  minutes. 

4.  Now  gradually  admit  more  and  more  oxygen  and  note 


120  EXPERIMENTAL   PHARMACOLOGY 

carefully  the  recovery  symptoms.  What  principles  are  in- 
volved in  nitrons  oxide  analgesia  or  anesthesia  ?  How  long 
does  it  take  the  animals  to  become  normal!  How  does  this 
compare  with  ether? 

5.  Eemove  the  alkali  and  allow  the  animals  to  become 
normal,  or  much  better,  get  two  fresh  animals  (a  small  tur- 
tle may  also  be  included  if  the  bottle  is  large  enough)  and 
then  with  the  animals  in  the  bottle  run  in  a  little  CO2.  Note 
the  changes  in  rate  and  depth  of  respiration  if  any  occur. 
Add  more  CO2.  Can  you  produce  an  anesthesia  with  00^.: 
Read  this  up  in  your  text.  Compare  the  symptoms  in  the 
two  (or  three)  animals.    Allow  the  animals  to  recover. 

6.  Paul  Bert's  Experiment. — Eeplace  the  alkali  in  the 
bottle  and  again  run  NaO  into  the  bottle  but  leave  the  outlet 
open.  In  this  way  wash  out  the  air  and  obtain  almost  a 
pure  atmosphere  of  N2O.  Bo  not  ivaste  any  more  gas  than  is 
necessary.  (As  soon  as  marked  symptoms  of  asphyxia  ap- 
pear add  a  little  oxygen.)  When  nearly  all  of  the  air  (nitro- 
gen) has  been  run  out  of  the  bottle  then  close  the  outlet  and 
wait  a  little  if  the  animals  are  not  unconscious  and  do  not 
show  too  marked  s>miptonis  of  asphyxia.  Then  slowly  raise 
the  pressure  in  the  bottle  by  admitting  oxygen.  Paul  Bert 
found  that  in  an  atmosphere  consisting  of  eighty  per  cent 
N2O  and  twenty  per  cent  oxygen,  but  with  the  pressure 
raised  one-fourth  above  the  normal  atmospheric  pressure,  a 
complete  nonasphyxial  anesthesia  could  be  produced  and 
maintained  indefinitely.  Can  you  repeat  his  experiment? 
What  gas  does  an  animal  give  off  in  its  expired  air?  What 
is  the  fate  and  mode  of  excretion  of  absorbed  nitrous  oxide? 
In  what  form  is  it  carried  in  the  blood?  Plow  does  this 
compare  with  ether  and  chloroform  or  ethyl  chloride  or 
ethyl  bromide?  What  is  the  purpose  of  the  alkali  in  these 
experiments  ? 

7.  Allow  the  animals  to  recover  (or  obtain  fresh  ones). 
Place  them  in  the  bottle  (the  alkali  should  also  be  in)  and 


CLOSED  METHOD  OF  AIS^ESTHESIA  121 

then  inject  a  small  amount  of  ethyl  chloride  vapor.  This  is 
best  done  with  a  Gebaner  tnbe  as  shoA\Ti  in  the  picture  but 
other  containers  which  may  be  used  are  also  in  the  market 
(Fig.  54).  If  ampoules  are  used  the  neck  should  be  tiled 
a  little  and  then  the  entire  neck  end  of  the  ampoule  is  in- 
serted like  a  cork  (air  tight)  into  the  rubber  tube  going  into 
the  bottle.  The  outlet  is  opened  and  the  neck  of  the  ampoule 
is  snapped  off  by  bending  the  tube.  The  ethyl  chloride  is 
very  volatile  and  at  once  rushes  into  the  bottle.  Wait  a  lit- 
tle while  for  the  drug  to  act.  It  generally  acts  fairly  rap- 
idly but  ma}^  require  a  little  time  for  diffusion  through  the 
bottle  and  absorption  into  the  animals'  blood.  How  do  the 
s^anptoms  compare  Avith  those  produced  by  ether  or  chloro- 
form! How  long  does  it  take  to  produce  complete  anesthe- 
sia ?  If  3^ou  add  oxygen  as  needed,  how  long  can  you  keep  up 
this  anesthesia  with  one  dose  of  ethyl  chloride  ?  Do  not  give 
more  ethyl  chloride  than  is  absolutely  necessary  or  you  may 
kill  one  or  both  of  the  animals.  "Somnoform"  or  Brugg's 
mixture  may  be  used  also  if  the  drugs  are  available  (they 
can  be  bought  from  dental  supply  houses  and  are  put  up  in 
ampoules).  Similarly  ethyl  bromide  may  be  used.  A  small 
quantity  of  this  may  be  poured  into  the  bottle  through  a 
funnel.  Save  all  animals  used  until  next  day  and  observe  if 
any  permanent  injury  has  been  done  to  them. 

EXPERIMENT  VIII. 

The  Closed  Method  of  Anesthesia.    For  Ether,  Chloroform, 

Ethyl  Chloride,  Ethyl  Bromide,  (Nitrous  Oxide), 

' '  Somnof orm, "   etc.,  with  Oxygen.     Student 

Method.     (Dogs  or  Cats.) 

1.  Observe  carefull}^  the  construction  of  the  apparatus 
shown  in  Fig  116.  Arrange  the  table  for  operative  work 
as  shown  in  Fig.  117,  but  omit  the  ether  bottle,  substituting 
therefor  the  apparatus  sho^vii  in  the  illustration.    Into  the 


122 


EXPERIMENTAL   PHARMACOLOGY 


bottom  of  the  large  pan  shown  in  Fig.  116  pour  a  layer  of 
strong  (not  saturated)  sodium  (or  potassium)  hydrate  solu- 
tion al30ut  three-fourths  inch  deep.  The  solution  must  not 
he  IV arm.  Stretch  the  thin  rubber  bath  cap  air-tight  over 
the  rim  of  the  large  pan  as  illustrated.  Thereafter  do  not 
upset  the  pan  nor  splash  out  the  solution.    If  the  dog  strug- 


Wheei  wrench 


Fig.  116. — Apparatus  used  for  closed  ether  (ethyl  chloride,  chloroform,  nitrous  oxide, 
etc.)  anesthesia.  A  large,  shallow,  round  cake  pan  covered  by  a  thin  bath  cap  holds 
the  vapors  or  gases.  The  animal  breathes  into  and  out  of  the  pan  through  a  spout. 
Strong  sodium  (or  potassium)  hydrate  solution  (which  must  be  cold)  in  the  bottom  of 
the  pan  absorbs  the  CO2  eliminated.  A  diagrammatic  view  of  the  pan  as  seen  from  above 
is  shown  in  Fig.  118.  Oxygen  is  admitted  as  needed  by  the  animal  from  the  tank  (or 
from  the  apparatus  shown  in  Figs.  176  and  177).  Ether  or  chloroform  or  ethyl  bromide 
may  be  injected  through  the  burette.  Ethyl  chloride  can  be  sprayed  in  through  one  of 
the  inlets.  (See  Journal  of  Laboratory  and  Clinical  Medicine,  1916,  ii,  p.  94;  also  ibid., 
1916,  ii,  p.   145.) 

gles  this  might  occur,  but  such  an  accident  is  much  more 
likely  to  happen  as  the  result  of  awkwardness.  Etherize 
the  dog  on  the  floor  in  the  usual  manner  (Fig.  71).  Then 
place  it  quickly  on  the  operating  board,  tie  it  do^vn  and 
insert  the  tracheal  cannula.     The  straight  end  of  the  can- 


CLOSED  METHOD  OF  AISIESTHESIA  12.5 

iiula  carries  a  short  piece  of  rubber  tubing  and  a  screw 
clamp.  Close  the  clamp  and  insert  the  side  tube  of  the  can- 
nula into  the  hole  in  the  cork,  which  closes  the  large  spout 
from  the  pan.  Run  enough  oxygen  into  the  pan  to  lift  the 
bath  cap  up  about  one  inch  above  the  top  of  the  large  pan. 
From  the  burette  it  will  probably  be  necessary  to  inject 
about  one  or  two  cubic  centimeters  of  ether  into  the  pan  be- 
fore the  anesthesia  becomes  deep  enough.  Do  not  be  in 
too  much  of  a  hurry  to  add  this  ether,  for  the  anesthesia 
should  not  be  any  deeper  than  is  necessary.    Hereafter  the 


Wash  jar         Ether  bottle 


injecting  burette 
5teft\ogr3ph 


Ligatures 


Artificial 
respiration 


Small  table 

r.nn. 


Liqa  tares 


6in.Tinner's snips  Trephine 


Fiij.    117. — Arrangement    of    the    apparatus    on    the    table    for    performing    an    experiment. 

anesthetist  merely  watches  to  keep  a  fair  amount  of  ox^^gen 
in  the  pan  and  at  long  intervals  from  one-half  to  one  cubic 
centimeter  of  ether  may  be  injected  if  needed.  The  anes- 
thesia should  remain  perfectly  constant  and  regular  if  no 
leaks  are  present  in  the  apparatus.  These  are  not  difficult 
to  avoid.  If  the  experiment  is  performed  correctly  the  stu- 
dent will  be  impressed  with  the  ease  and  certainty  with 
which  a  perfect  anesthesia  can  be  maintained  for  long  per- 
iods of  time.  If  too  much  ether  (or  other  anesthetic)  gets 
into  the  pan  open  the  screw  clamp  on  the  tracheal  cannula 


124 


EXPERIMENTAL   PHARMACOLOGY 


and  allow  some  of  the  vapor  to  escape.  Then  refill  the  pan 
with  oxygen.  This  method  is  new.  Students  are  advised  to 
study  it  carefully.  Is  there  any  danger  of  the  respiratory 
medium  becoming  too  moist?  Are  any  volatile  poisons 
given  off  in  the  breath  that  might  accumulate  in  the  breath- 
ing space?  Will  the  smaller  percentage  of  nitrogen  in  the 
air  breathed  by  the  animal  influence  the  anesthesia  ?    Will 


Eiher 
inlet 


Oxyqen 
inlet 


Flanqe 
< Lower  flanqe 


Fig.    118. — Diagrammatic  view   of   the   pan   as   seen   from   above. 

the  respiratory  medium  become  too  warm!  Could  you 
counteract  this?  How  is  the  ether  excreted!  How  is  it 
absorbed  and  carried  to  the  tissues?  W^hat  combinations 
does  it  form  in  the  body? 

2.  Arrange  to  record  blood-pressure  and  respiration 
(stethograph).  Connect  an  injecting  burette  to  the  left 
femoral  vein.  Isolate  and  ligate  loosely  (but  do  not  clamp 
or  injure)  the  right  femoral  artery.  Place  some  adrena- 
line (1:10,000)  solution  in  the  burette.  Or  epinine  solu- 
tion (1:1000,  Burroughs,  Wellcome  and  Co.)  may  be  used. 


CLOSED  METHOD  OF  ANESTHESIA 


125 


126 


EXPERIMENTAL   PHARMACOLOGY 


Arrange  all  writing  points  on  the  drum  and  take  a  few 
inches  of  normal  record.  How  does  this  record  of  blood- 
pressure  and  respiration  compare  with  that  obtained  when 
you  used  an  ordinary  ether  bottle  to  maintain  the 
anesthesia? 

3.  While  the  anesthesia  is  moderately  light  but  per- 
fectly regular,  inject  just  enough  oxygen  to  run  the  animal 
for  about  three  minutes.  Then  with  a  screw  clamp  close 
off  the  injecting   (oxygen)   tube  and  change  the  oxygen 


Fig.  120. — At  the  place  marked  "normal"  the  animal  was  breathing  naturally.  No 
drug  had  been  administered  and  the  animal  was  lying  quietly  on  the  table.  At  the  point 
indicated  some  nitrous  oxide  was  given.  The  respiration  at  once  becomes  deeper  and 
more   rapids 


tank  for  a  nitrous  oxide  tank.  Open  the  screw  clamp  on 
the  injecting  tube  and  run  in  as  much  N2O  as  is  possible 
without  stretching  the  bath  cap.  This  should  be  perfectly 
free  to  rise  and  fall  and  should  not  be  under  any  tension. 
If  the  cap  is  stretched  the  animal  cannot  breathe  well  for 
the  mechanical  obstruction  and  may  die.  The  drum  runs 
at  a  slow  speed  as  the  N2O  is  run  in.  How  does  this  affect 
the  blood-pressure  and  respiration!  How  does  this  com- 
pare with  the  injection  of  a  drug  through  the  femoral  vein? 


CLOSED  METHOD  OF  AISTESTHESIA 


127 


What  is  the  action  of  N2O  on  the  heart  I    Is  the  anesthesia 
deepened? 

4.  After  a  sufficient  time  open  the  side  clip  from  the  pan 
and  empty  out  the  mixed  gases.  Close  the  clip  and  run 
in  some  fresh  oxygen.  Take  some  more  normal  record 
and  then  from  a  Gebauer  ethyl  chloride  tube  inject  through 
the  outlet  tube  of  the  pan  a  small  amount  of  ethyl  chloride. 


Fig.  121. — The  animal  was  anesthetized  with  nitrous  oxide.  At  the  point  indicated 
a  little  ethyl  chloride  was  given  (in  addition  to  the  nitrous  oxide).  The  much  more 
marked  action   of  ethyl   chloride   on   the   blood-pressure   and   respiration   is   seen  at   once. 


Do  not  give  too  much.  How  does  this  affect  the  blood- 
pressure  and  respiration!  Is  the  anesthesia  deepened? 
Which  is  the  more  powerful,  ether  or  ethyl  chloride! 
Empty  out  the  ethyl  chloride  and  allow  the  anesthesia  to 
become  fairly  light. 

5.  Eepeat  No.  4,  using  ethyl  bromide,  ''somnoform"  or 
Brugg's  mixture  instead  of  ethyl  chloride.     Do  not  give 


128  EXPERIMENTAL   PHARMACOLOGY 

more  than  one  cubic  centimeter  of  ethyl  'bromide  (one-half 
cubic  centimeter  is  mucli  safer).    This  is  a  powerful  drug. 

6.  After  records  are  obtained  empty  out  the  vapors, 
open  the  screw  clamp  on  the  tracheal  cannula  and  allow 
the  dog  to  get  fresh  air  for  some  time  to  recover.  (The 
animal,  of  course,  thus  exhales  the  drugs  into  the  open 
air.) 

7.  When  the  animal  recovers  close  the  tracheal  clamp 
and  let  the  anesthesia  again  become  as  regular  as  pos- 
sible. Now  through  the  burette  inject  into  the  pan  one- 
half  cubic  centimeter  of  chloroform.  Do  not  give  too  much. 
Obtain  a  record  and  then  empty  out  the  vapor  as  before. 
How  does  this  record  compare  with  those  obtained  with 
the  other  drugs  ?  What  conclusions  can  you  draw  concern- 
ing chloroform?  What  class  of  physicians  make  most  use 
of  chloroform? 

Can  you  use  the  closed  method  for  anesthesia  when  the 
chest  is  opened?  This  is  a  good  point  for  the  student  to 
consider.  Does  this  method  present  any  advantages  over 
the  use  of  an  ordinary  ether  bottle  ?  What  are  the  relative 
disadvantages? 

8.  Put  about  one  cubic  centimeter  of  chloroform  into  a 
good  dental  syringe  carrying  a  small  short  needle.  Now 
lift  up  the  right  femoral  artery  on  an  aneurism  needle  and 
at  the  same  time  let  an  assistant  press  down  on  the  cor- 
responding vein  to  shut  off  its  return  flow.  Now  with 
great  care  slip  the  syringe  needle  endwise  into  the  lumen 
of  the  artery.  Loosen  the  tension  on  the  artery  a  little 
and  as  the  blood  again  flows  through  carefully  inject  the 
chloroform.  Feel  of  the  leg.  Is  there  produced  a  pro- 
found change  in  the  tissues?  If  not,  repeat  the  injection 
into  the  other  femoral  artery. 

9.  Kill  the  dog  by  asphyxia.  Open  the  abdomen  and 
dissect  out  and  examine  the  spleen,  pancreas  and  left  kid- 
ney.   To  what  is  the  spleen  attached?    Place  it  inside  an 


INTKATRACHEAL    1:^811  FFLATION 


129 


oncometer  and  close  the  abdomen  with  hemostats.  Could 
you  do.  this  in  a  living  dog?  Eemove  the  oncometer  and 
put  away  all  apparatus.  Do  not  forget  to  wash  out  the 
tubing  connecting  the  carotid  to  the  manometer. 

EXPERIMENT  IX. 
Intratracheal  Insufflation. 

1.  Study  carefully  the  principles  involved  in  the  con- 
struction of  the  apparatus  shown  in  Fig.  122.    A  constant 


Fig.  122. — Apparatus  for  intratracheal  insufflation.  The  tip  of  the  catheter  should 
Ibe  cut  off  just  back  of  the  "eye."  Any  similar  sized  rubber  tube  may  be  used  instead 
•of  the  catheter.  The  outer  diameter  of  the  tube  should  be  about  one-half  (or  a  little 
Jess  than)    that  of  the  inner  diameter  of  the  trachea. 

■current  of  air  passes  into  the  tube  at  the  extreme  right  of 
the  picture.  By  turning  the  small  lever  on  the  side  of  the 
-ether  valve,  part  or  all  (or  none)  of  the  air  can  be  made  to 
pass  over  the  ether  and  then  out  through  the  rubber 
<catheter  at  the  left.     (The  cap  and  spout  on  the  top  of  the 


130 


EXPERIMENTAL   PHARMACOLOGY 


ether  valve  are  not  used  in  this  experiment.  The  opening 
up  into  the  cap  should  be  closed  with  a  cork.)  Any  ordi- 
nary ether  bottle  with  a  side  pass  as  shown  in  Fig.  107  may 
be  used  for  this  purpose  instead  of  the  valve  here  shown. 
Just  to  the  left  of  the  ether  bottle  is  a  smaller  bottle  con- 
taining mercury.    The  cork  in  this  bottle  is  perforated  by 


-Flexible 
Breoihinq 
Bac] 

Metallic  muzzle 
with  rubber  cushion 


Fig.  123. — Schematic  arrangement  of  an  apparatus  for  administering  nitrous  oxide 
(ether,  etc.)  to  an  animal.  The  gas  or  vapor  (ether)  is  washed  (by  means  of  the  air 
pump)  through  NaOH  solution  (to  remove  CQo)  and  through  H2SO4  (to  remove  watery 
vapor).  Oxygen  is  admitted  as  needed  by  the  animal.  The  animal  breathes  into  and 
out  of  the  ventilated  bag. 

two  holes  through  one  of  which  a  tube  from  the  main  air 
way  dips  down  just  below  the  surface  of  the  mercury. 
This  tube  can  be  raised  or  lowered  and  thus  serves  as  an 
adjustable  pop-off  valve  to  regulate  the  pressure  if  it  be- 
comes too  great.  To  the  left  of  the  mercury  bottle  a  mer- 
cury manometer  and  scale  are  placed.     The  manometer 


ACTIOIsr  OF  CARBON  DIOXIDE 


131 


132  EXPERIMENTAL   PHARMACOLOGY 

connects  with  the  main  air  way  and  when  in  nse  the  mer- 
cury manometer  should  record  a  pressure  of  about  twenty 
millimeters. 

For  an  average  sized  dog  the  catheter  may  have  an  out- 
side diameter  of  about  three-sixteenths  or  one-fourth  inch. 
The  catheter  is  slipped  into  the  trachea  do^vn  to  its  bifur- 
cation and  then  withdrawn  a  little.  The  animal  should  be 
etherized  in  the  usual  manner  and  then  the  catheter  may 
be  introduced  through  the  larynx  or  through  the  tracheal 
cannula.  The  air  and  ether  vapor  blown  in  through  the 
catheter  escapes  again  from  the  lungs  between  the  outer 
wall  of  the  catheter  and  the  inner  wall  of  the  trachea. 
As  a  rule,  the  dog  Avill  keep  up  shallow  respiratory  move- 
ments while  the  anesthesia  is  carried  on  by  this  method. 
Would  it  be  advisable  to  turn  the  air  current  off  for  a 
few  seconds  at  intervals  of  one  or  two  minutes?  It  is  ad- 
visable for  the  student  to  practice  for  some  time  with  this 
method  before  attempting  severe  operations  while  using 
it.  Meltzer,  Auer  and  their  associates  at  the  Rockefel- 
ler Institute  have  extensively  used  and  developed  this 
method,  while  from  the  University  of  Minnesota  Hirsch- 
felder  has  reported  excellent  results  with  it  in  ordinary 
student  experiments.  Can  3^ou  repeat  these  results'?  Could 
this  method  be  used  when  the  chest  is  opened?  What  pre- 
cautions would  you  then  take  ?  Could  you  use  the  method  to 
record  changes  in  the  volume  of  the  lungs  (see  Figs.  187 
and  257,  also  consult  Experiments  XXIX  and  LXX). 

What  are  the  advantages  of  this  method?  What  are 
the  disadvantages?  This  method  may  be  used  in  some  of 
the  later  experiments.  It  is  often  very  convenient  for 
maintaining  a  regular  anesthesia. 

This  method  has  been  much  used  for  intrathoracic  sur- 
gery, etc.,  and  several  different  forms  of  apparatus  for 
carrying  on  intratracheal  insufflation  have  been  devised 
and  used.  It  is  very  desirable  for  the  student  to  become 
familiar  with  the  principles  involved,  and  if  possible,  to 
have  some  experience  in  using  the  method. 


GENERAL  ACTION   OF  ALCOHOL 


EXPERIMENT  X. 


Alcohol.    (Frog:  Central  Nervous  System,  Heart  and  Vago- 
sympathetic Nerve.) 

1.  Solutions  of  alcohol  for  injections  or  administration 
by  stomach  shonlcl,  if  possible,  be  made  up  from  absolute 
alcohol.  For  the  technic  of  injecting  solutions  into  the 
lymph  spaces  of  frogs  see  Figs.  125  and  126.  Make  up 
nine  cubic  centimeters  of  alcohol  66  2/3  per  cent  strong. 
Into  the  anterior  lymph  sac  of  a  frog  inject  either  from  a 
glass  injecting  pipette  (Fig  127)  or  with  a  hypodermic 
syringe  (Fig.  126)  one  cubic  centimeter  of  the  alcohol  so- 
lution. Do  not  injure  the  frog  in  any  way  in  holding  it, 
etc.  Place  the  animal  in  a  battery  jar  on  some  moist  cot- 
ton and  observe  its  actions  closely.  Touch  it  from  time 
to  time  to  observe  the  condition  of  the  reflexes.  Does  the 
animal  show  any  symptoms  from  the  local  irritation  of 
the  drug  at  the  point  of  injection?  Do  these  obscure  the 
later  systemic  effects  which  come  on  after  absorption  of 
the  drug  by  the  circulation!  How  do  the  symptoms  pro- 
duced by  alcohol  compare  with  those  produced  by  ether  or 
chloroform  or  nitrous  oxide!  What  organs  are  affected 
by  alcohol  as  shown  b}^  this  experiment!  Does  the  frog- 
become  completely  narcotized!  If  so,  how  long  does  the 
condition  last!  Does  the  animal  recover  completely! 
Place  it  in  a  battery  jar  on  moist  cotton  for  several  hours 
to  allow  of  recovery.  The  beating  of  the  heart  can  be 
seen  through  the  chest  wall  in  front. 

2.  Pith  a  frog  and  dissect  out  the  vagus  nerve.  Place 
the  electrodes  so  that  the  nerve  can  be  stimulated  without 
disturbing  the  animal  and  arrange  for  taking  a  heart  trac- 
ing. Take  two  inches  of  normal  tracing  and  then  stimulate 
the  vagus  nerve.  Do  you  get  a  normal  inhibition!  (Do 
not  stimulate  the  nerve  too  long  or  too  often  or  you  ^\dll 
wear  it  out.    You  can  not  then  test  tlie  action  of  tlie  drug 


134 


EXPEEIMENTAL   PHARMACOLOGY 


on  the  inhibitory  mechanism.)     It  is  usually  advisable  to 
take  two  records  of  normal  vagus  inhibition. 

Now  start  a  second  round  of  the  tracing  and  when  the 
new  record  lacks  about  one  inch  of  being  directly  over 


Fig.    125. 


Fig.    126. 


Fig.  125. — Injection  of  drug  solutions  into  the  anterior  lymph  sac  of  a  frog.  The 
narrow  point  of  the  injecting  pipette  is  passed  into  the  mouth,  and  the  tongue  (which 
is  attached  to  the  front  part  of  the  lower  jaw)  is  pushed  to  one  side.  The  point  of  the 
pipette  is  quickly  but  gently  forced  through  the  muscles  in  the  floor  of  the  mouth.  The 
point  will  then  be  felt  just  beneath  the  skin  over  the  under  jaw.  The  pipette  is  now 
slipped  down  toward  the  chest.  The  skin  is  attached  to  the  underlying  muscles  across 
the  sternum  but  the  point  is  passed  through  this  attachment  and  into  the  lymph  space 
in  front  of  the  abdomen.  The  finger  is  taken  off  of  the  upper  end  of  the  pipette  and 
the  solution  is  allowed  to  run  slowly  into  the  anterior  lymph  sac.  Do  not  injure  the 
frog  by  squeezing  it. 

Fig.  126. — Injection  of  solutions  into  the  anterior  lymph  sac  with  a  small  hypodermic 
syringe. 

the  first  vagus  inhibition  record,  drop  on  the  heart  about 
ten  drops  of  ten  per  cent  alcohol.  How  does  this  affect 
the  beat  of  the  organ?    At  the  moment  when  the  record 


ACTION   OF   ALCOHOL  135 

reaches  a  place  directly  over  the  first  inhibition  record, 
stimulate  the  vagus  nerve  again.  Do  you  now  get  an  in- 
hibition, or  has  the  drug  paral^^zed  some  part  of  the  local 
inhibitory  apparatus'?  Drop  on  more  alcohol  and  again 
stimulate  the  nerve  over  the  second  inhibitory  record.  The 
total  length  of  the  record  from  left  to  right  should  be 
about  seven  or  eight  inches  with  a  moderate  drum  speed. 
About  five  or  six  rounds  of  tracing  (in  a  series  from  the 


:r:::;::j0immlm^ 


Fig.     127. — Injecting    pipette    made    of    glass.      About    2/3    natural    size. 

bottom  of  the  drum  upwards)  should  be  made.  Add  the 
alcohol  freely  to  the  heart  during  the  second  and  third 
rounds,  but  on  the  later  rounds,  if  necessary,  use  thirty  or 
forty  per  cent  alcohol.  What  is  the  general  action  of  alco- 
hol on  the  frog's  heart  as  shown  by  your  tracing?  Does 
alcohol  either  paralyze  or  stimulate  the  inhibitory  appa- 
ratus?   How  does  this  compare  with  ether  or  chloroform? 


EXPERIMENT  XI. 
Alcohol.     (Turtle:  Heart  and  Vagus  Nerve.) 

1.  Pith  a  turtle  and  fasten  it  dowm  to  the  turtle  board. 
Expose  the  heart  and  take  a  heart  tracing  (normal)  includ- 
ing two  or  three  vagus  inhibitory  records.  Then  apply 
twenty  per  cent  alcohol  to  the  heart  as  Avas  done  in  Experi- 
ment X,  and  again  stimulate  the  nerve.  What  effect  does 
the  drug  have  on  the  local  inhibitory  apparatus?  If  the 
heart  muscle  alone  should  be  stimulated  by  the  drug  would 
the  inhibition  be  greater  or  less  when  the  nerve  was  stim- 
ulated after  the  drug  was  applied  ?  How  would  the  inhibi- 
tion be  affected  if  the  muscle  alone  were  depressed? 


136  EXPERIMENTAL   PHARMACOLOGY 

EXPEEIMENT  XII. 

Ethyl  Alcohol,  Brandy,  Whiskey,  Wine,  Methyl  Alcohol, 

Amyl  Alcohol.     (Dog:  Blood-pressure,  Respiration, 

Esophagus.) 

1.  Etherize  a  dog  and  arrange  for  blood-pressure  and 
respiratory  tracings.  Connect  injecting  burettes  to  both 
femoral  veins.  Isolate  and  ligate  loosely  both  vagi,  using 
great  care  not  to  injure  them  in  the  dissections  or  manip- 
ulation or  by  allowing  a  part  of  either  nerve  to  lie  outside 
the  wound  and  to  become  so  much  dried  up  in  the  air  that 
impulses  can  no  longer  be  conducted  over  the  nerve  fibers. 

Now  pull  the  trachea  to  the  left  side  and  pick  up  the 
esophagus  (pulling  it  toward  the  right)  on  a  large  aneu- 
rism needle.  Make  a  longitudinal  incision  about  three- 
fourths  of  an  inch  long  in  the  side  of  the  esophagus  a  little 
way  below  the  larynx.  Now  pass  through  this  incision  into 
the  lumen  of  the  esophagus  the  finger  cot  on  the  end  of 
the  catheter  as  shown  in  Fig.  128.  The  end  of  the  cathe- 
ter should  pass  doAvti  the  esophagus  to  a  point  about  one 
or  two  inches  above  the  cardiac  sphincter.  A  ligature  is 
then  tied  around  the  catheter  at  the  esophagus  incision 
tight  enough  to  prevent  the  catheter  from  slipping  out 
and  with  a  hemostat  the  ligature  ends  are  clamped  (close 
to  the  esophagus)  to  the  neck  tissues  at  the  side  of  the 
wound.  The  burette  is  now  filled  about  half  full  of  wa- 
ter and  the  catheter  is  moved  in  and  out  a  little  to  get 
the  water  to  run  down  into  the  finger  cot.  It  is  important 
for  the  cot  to  be  ivell  filled  ivith  the  ivater.  Place  the  cork 
in  the  burette  and  connect  the  tube  in  the  cork  to  a  medium 
sized  tambour  AA^hich  is  adjusted  for  a  fairly  large  magnifi- 
cation. Arrange  this  tambour  to  write  at  the  top  of  your 
records ;  next  below  this  should  be  the  blood-pressure 
(manometer)  record,  below  this  the  respiration,  and  at 
the  bottom  should  be  the  base  line  marked  by  a  signal 


RECORDING  ESOPHAGEAL  COXTRACTIOXS  16  ( 

magnet  whicli  records  five  or  ten  second  intervals.  If  a 
metronome  or  Harvard  clock  is  used,  shorter  time  inter- 
vals must  be  employed.  This  may  call  for  a  faster  drum 
speed.     The  rate  should,  however,  be  fairly  slow.     When 


Fig.     128. — Arrangement     of     apparatus     for     recording     esophageal     contractions. 


all  adjustments  are  made  start  the  drum  and  record  one 
or  two  inches  of  normal  tracing.  Then  with  a  medium 
strength  tetanizing  current  stimulate  the  right  vagus  nerve 
for  one-half  second.     Wait  till  the  records  all  return  to 


138 


EXPERIMENTAL   PHARMACOLOGY 


normal  and  then  stop  the  drum.  Does  the  vagus  stimula- 
tion stop  the  heart?  How  does  it  affect  the  respiration? 
Did  you  get  a  record  from  the  esophagus?  If  so,  how  do 
you  explain  the  cause  of  this  last  record?  Could  the  record 
have  been  caused  hy  the  respiratory  movements?     Could 


MCcXM 


\SU4^UAatii<nv' 


mlmmi 


Fig.    129. — Four  esophageal   contractions,   blood-pressure   and   respiration.      The    nerve   was 
stimulated   (for  a  moment  only)    four  times  by  a  tetanizing  current. 


ACTION   OF  ALCOHOL  139 

yon  avoid  this  possibility  in  any  way?  Is  the  superior 
laryngeal  nerve  concerned  in  any  way  with  your  observa- 
tions? Stimulate  this  nerve  independently  and  study  the 
results. 

Place  adrenaline  solution  in  one  injecting  burette  and 
twenty  per  cent  alcohol  (made  from  absolute  alcohol)  in 
the  other.  Start  the  drum  and  when  about  one  inch  of 
satisfactory  normal  tracing  has  been  taken  inject  two  cubic 
centimeters  of  the  alcohol  solution.  The  blood-pressure 
and  respiration  are  slightly  affected.  This  gives  you  a  fair 
basis  to  estimate  the  resistance  of  the  animal  to  the  alco- 
hol and  to  judge  what  size  the  next  dose  should  be.    If  the 


Fig.    130. — Harvard    membrane    manometer. 

dog  is  small  or  very  susceptible  the  dosage  must  be  re- 
duced. When  the  records  have  returned  to  normal  inject 
as  large  a  dose  as  you  think  the  animal  can  safely  stand 
and  yet  make  a  good  recovery.  This  will  likely  range 
between  five  and  fifteen  cubic  centimeters  but  may  be  much 
larger  in  many  cases.  Secure  two  or  three  good  tracings 
from  alcohol  and  then  again  stimulate  one  vagus  nerve  for 
a  brief  period.  When  the  records  return  to  normal  stop 
the  drum.  How  do  the  records  obtained  now  compare 
with  those  made  before  the  drug  was  given?  If  the  ani- 
mal seems  very  weak  or  about  to  die  inject  one-half  cubic 
centimeter  of  adrenaline. 

2.  Enipt}'-  the  alcohol  out  of  the  burette  (give  it  back  to 


140  EXPEEIMENTAL   PHARMACOLOGY 

the  instructor)  and  fill  the  burette  with  brandy.  What  is 
the  percentage  of  alcohol  in  brandy?  How  is  brandy  made? 
Start  the  drum  and  inject  what  you  believe  Avill  be  a  fair 
sized  dose  for  your  animal.  Do  this  two  or  three  times 
and  secure  satisfactory  tracings.  How  do  these  tracings 
compare  with  those  obtained  from  alcohol? 

3.  Replace  the  brandy  in  the  burette  with  whiskey. 
What  is  the  percentage  of  alcohol  in  whiskey?  Inject  a 
fair  sized  dose  and  secure  satisfactory  tracings.  This  may 
be  done  two  or  three  times  if  the  animal  is  sufficiently  re- 
sistant. But  if  the  animal  is  weak,  then  the  fewest  injec- 
tions possible  should  be  given  to  secure  typical  tracings 
showing  the  action  of  each  drug. 

4.  Substitute  wine  for  the  whiskey  in  the  burette.  How 
much  alcohol  is  there  in  wine?  What  else  is  contained  in 
wine?  Inject  one  or  two  cubic  centimeters  and  see  how 
this  affects  the  animal.  Use  larger  doses  if  you  can  safely 
do  so.  How  do  the  records  obtained  compare  with  those 
from  alcohol,  brandy  and  whiskey  ?  How  do  you  explain 
this?  Inject  some  adrenaline  and  then  allow  the  animal 
to  recover. 

5.  Fill  the  burette  with  twenty  per  cent  methyl  alcohol. 
Inject  one  cubic  centimeter  and  secure  a  record.  How 
does  the  toxicity  of  this  drug  compare  with  that  of  ethyl 
alcohol?  If  it  appears  safe,  a  larger  dose  may  be  injected 
to  secure  satisfactory  tracings.  Does  the  alcohol  which 
you  have  injected  affect  the  anesthesia  in  any  way? 

6.  Substitute  a  ten  per  cent  mixture  (shake  well)  of 
amyl  alcohol  and  water  for  the  methyl  alcohol  in  the  bu- 
rette. Inject  one-half  cubic  centimeter  and  secure  trac- 
ings. What  can  you  say  about  the  toxicity  of  this  body? 
Kill  the  animal  mth  amyl  alcohol.  "W^ich  stops  first,  the 
heart  or  the  respiration?  Give  some  adrenaline,  massage 
the  heart  and  give  artificial  respiration  to  see  if  you  can 
revive  the  animal.    It  is  important  for  the  student  to  learn 


PRACTICE    DISSECTIONS 


141 


the  methods  used  for  reviving  animals  when  they  are  near 
death,  especially  from  threatened  death  under  an  anes- 
thetic. 


Fig.   131.— Arrangement  of  apparatus  which  may   be  used   as  a  membrane  manometer. 

7.  If  time  permits  after  the  animal  is  dead,  open  the 
chest  by  a  median  longitudinal  incision,  sawing  the  ster- 


Fig.  133. — Dissection  showing  the  vessels  and  nerves  in  the  neck  and  upper  part  of 
the  chest  in  a  dog.  (Modified  from  Schmiedeberg.)  1.  Rt.  inferior  (recurrent)  laryngeal 
nerve.  2.  Vago-sympathetic  nerve.  3.  Phrenic  nerve.  4.  Vertebral  nerve.  S.  Rt.  in- 
ferior (recurrent)  laryngeal  nerve.  6.  Inferior  cervical  ganglion.  7.  Cerv'ical  sympa- 
thetic nerve.  8.  First  thoracic  ganglion.  9.  Superior  cardiac  nerve.  10.  Inferior 
cardiac  nerve.  11.  Vagus  trunk.  12.  External  jugular  vein.  13.  Thyroid  gland.  14. 
Internal  jugular   vein.      15.    Subclavian   artery.      16.    Carotid   artery.      17.    Brachial   plexus. 


PRACTICE   DISSECTIONS  143 

num  open  endwise,  and  make  the  following  observations : 
Isolate  and  trace  out  both  phrenic  nerves.  Trace  the 
vago-sympathetic  trunks  from  the  neck  region  doAvn  into 
the  chest.  Follow  the  right  nerve  closely  in  the  tissues  at 
the  apex  of  the  chest.  At  this  point  isolate  the  subclavian 
vein  and  tie  two  ligatures  tightly  around  the  vessel.  Be 
sure  the  ligatures  are  tied  tightly  enough  not  to  slip  off. 
Cut  the  vein  between  the  ligatures  and  follow  the  nerve 
down  behind  the  vein  to  the  subclavian  artery.  (See  Figs. 
133  and  184.)  Isolate  the  annulus  Vieussenii  (ansa  sub- 
clavia)  and  pick  up  the  fibers  that  pass  off  toward  the 
heart.  Part  of  these  fibers  are  from  the  vagus  proper  and 
if  stimulated  in  the  living  animal  will  slow  or  weaken  (or 
stop)  the  beating  of  the  heart.  A  few  of  the  remaining 
fibers  are  from  the  sympathetic  system  (Figs.  148  and  318) 
and  when  stimulated  in  the  living  animal  will  cause  the 
heart  to  beat  faster  (accelerators)  or  stronger  (augmen- 
tors).  Could  you  perform  a  dissection  like  this  in  a  living 
animal?  What  Avould  be  the  most  likely  causes  of  failure? 
How  could  you  avoid  these?  Open  the  pericardium,  ex- 
amine the  auricles  and  ventricles.  Isolate  the  left  pul- 
monary artery  and  pass  a  ligature  beneath  it.  Hunt  for 
the  thoracic  duct.  "Where  is  it  located  in  the  chest  ?  What 
does  it  resemble?  With  what  might  you  confuse  it?  The 
writer  has  seen  students  look  in  the  wrong  side  of  the 
chest  for  the  duct.  What  criticism  would  you  offer  in 
such  a  case? 


EXPEKIMENT  XIII. 

Whiskey  or  Brandy.    (Reaction  Time.) 

1.  Observe  carefully  the  arrangement  of  the  apparatus 
shown  in  Fig.  134.  The  subject  of  the  experiment  holds 
do^vn  (closed)  the  handle  of  key  A;  key  B  remains  open. 
The  writing  point  of  the  signal  magnet  does  not  move. 


144 


EXPERIMENTAL   PHARMACOLOGY 


The  operator  holds  key  B.  The  drum  is  started  off  at  a 
fast  rate.  While  the  subject  watches  the  signal  magnet 
closely  the  operator  suddenl}^  closes  key  B.  The  writing 
point  of  the  signal  magnet  at  once  goes  down.  Instantly 
as  the  subject  sees  this  he  opens  key  A.  The  drum  keeps 
running,  the  operator  opens  key  B  and  the  subject  again 
closes  key  A.    The  operator  now  closes  key  B  and  the  sub- 


Fig.   134. — Arrangement  of  apparatus  for  recording  reaction  time  for  sight. 

ject  instantly  opens  key  A.  In  this  manner  about  twenty 
or  thirty  normal  records  are  taken.  With  a  vibrating 
tuning  fork  (Fig.  136)  beating  fiftieths  or  hundredths  of 
a  second,  a  time  tracing  (three  or  four  may  be  needed)  is 
now  run  around  the  drum.  With  a  pair  of  dividers  or  a 
rule  the  average  length  of  time  which  it  takes  the  subject 


EFFECT  OF  ALCOHOL  ON  REACTION  TIME 


145 


to  respond  to  a  sight  stimulus,  i.  e.,  his  normal  reaction 
time  for  sight,  is  estimated. 

The  subject  now  takes  by  stomach  five  or  ten  cubic  cen- 
timeters of  whiskey  or  brandy  well  diluted  with  water.    A 


Fig.    135. — Simple  key. 


little  sugar  may  be  added  to  the  water  in  order  to  in- 
duce the  subject  to  take  the  drug  more  readily.  After  fif- 
teen minutes  the  student's  reaction  time  for  sight  is  again 


Repldceabkforh 


Fig.    136. — Electric   tuning   foik. 


taken.     Is  there  any  change?     How  do  you  account  for 

this?    What  portions  of  the  nervous  system  are  involved! 

2.  Arrange  a  telephone  in  the  secondary  circuit  of  an  in- 


146 


EXPERIMENTAL   PHARMACOLOGY 


dnction  coil  as  shown  in  Fig.  137.  The  subject  holds  the 
telephone  to  his  ear  and  listens  (with  closed  eyes)  for 
the  click  of  the  closing  of  key  B  by  the  operator.  At  the 
instant  the  sonnd  is  heard  the  subject  opens  key  A.    The 


Key  A 


==!r^^""  KeyB 


Fig. 


137. Arrangement    of    apparatus    for    recording    reaction   time    for    hearing. 


reaction  time  for  sound  is  thus  recorded  on  the  drum.  Re- 
peat this  twenty  or  thirty  times  and  estimate  from  the 
tuning  fork  record  the  average  length  of  time  required  for 
the  reaction. 

The  subject  now  takes  some  whiskey  or  brandy  (or  wine) 
as  indicated  above  (1)  and  after  fifteen  minutes  his  reac- 


ALCOHOL,   WHISKEY,   BRANDY,   WINE 


147 


tion  time  is  again  taken.     Is  there  any  change?     What 
parts  of  the  nervous  system  are  concerned! 

3.  In  a  similar  manner  the  effect  of  alcoholic  drinks  on 
the  reaction  time  for  touch  may  be  recorded  by  allow- 
ing the  subject  to  place  his  finger  under  key  B  in  such  a 
manner  that  he  can  just  feel  the  closing  of  the  key  by  the 
operator.     The  subject  then  opens  key  A. 

4.  If  time  permits,  the  reaction  time  for  sight  and  sound 
may  be  taken  again  after  three  or  four  hours.  Compare 
these  results  ^vith  the  normals  and  with  those  obtained 
fifteen  minutes  after  the  drug  was  taken.  "What  conclu- 
sions can  you  draw? 

EXPERIMENT  XIV. 

Alcohol,  Whiskey,  Brandy,  Wine.     (Dog  or  Cat:  Myocar- 
diographic  Tracings,  Cardiac  Sympathetic  Nerves.) 

1.  Arrange  for  a  perfectly  constant  and  reliable  source 
of  artificial  respiration  before  beginning  the  experiment. 


Fig.     138. — Bo.x    for    anesthetizing    cats. 


If  a  cat  is  used,  all  the  cannulas  for  vessels  and  the  tra- 
chea must  be  much  smaller  than  those  used  for  dogs. 

Etherize  the  animal  in  the  usual  fashion.     If  a  cat  is 
used  it  may  be  etherized  in  a  special  box  (Fig.  138)  or  in 


148 


EXPERIMENTAL    PHARMACOLOGY 


a  bell  jar  (Fig.  139)  or  in  an  ordinary  earthenAvare  or 
glass  jar  covered  with  a  glass  plate.  A  tin  bread  box 
serves  very  well,  especially  if  it  has  a  glass  window.  Cot- 
ton ma}^  be  placed  in  the  neck  of  the  bell  jar  and  the 
ether  dropped  in  on  this.  If  a  box  like  Fig.  138  is  nsed,  the 
animal's  head  is  left  out  when  the  lid  is  closed  and  a  towel 
on  which  the  ether  is  dropped  is  placed  over  the  cat's 
head.  Cotton  saturated  with  ether  can  be  dropped  in  the 
earthenware  jar  or  bread  box. 


Fig.    139. 


Fig.    140. 


Fig.    139. — Bell-jar    as    used   for    anesthetizing    cats. 
Fig.    140. — Glass    or    earthenware    jar    covered    by    a    glass    plate.      Used    for    anesthetizing 

cats,   rabbits,   etc. 


Quickly  tie  the  animal  down  on  the  operating  board  and 
arrange  to  take  a  blood-pressure  tracing.  Connect  inject- 
ing burettes  to  both  femoral  veins.  Record  the  normal 
rectal  temperature.  By  a  median  incision  open  the  chest. 
In  a  cat  this  is  best  done  w^ith  tinner's  snips  (Fig.  98). 
(See  Fig.  105,  also  read  Experiment  V,  6,  page  108.)  When 
the  sterum  is  divided  throughout  its  length  pull  the  chest 


MYOCARDIOGRAPH 


149 


Fig.    141. — Myocardiograph. 


150 


EXPERIMENTAL  PHARMACOLOGY 


open,  tie  four  strong  ligatures  into  the  margins  of  the  sev- 
ered walls  as  shown  in  Fig.  106,  and  with  these  ligatures  tie 
the  chest  firmly,  leaving  an  opening  about  three  or  three 
and  one-half  inches  mde  in  a  dog.  This  opening  will  be 
smaller  in  a  cat.  Open  the  pericardium  and  stitch  it  to 
the  chest  walls. 


^To  recording 
tdtnbour 


Cdrdfomefer 


Pin  hook  fo  fasten  info 
ventricle 


Fig.  142. — Cai-diometer  arranged  for  use  as  a  myocardiograph.  The  pin  is  hooked 
into  the  heart  muscle  and  the  cardiometer  is  held  in  a  clamp.  The  beating  of  the  heart 
moves  the  membrane  in  and  out.     A  tambour  is  used  for  recording. 


Various  forms  of  instruments  are  used  to  record  heart 
tracings  directly  from  the  heart.  One  is  shown  in  Fig. 
141.  If  you  have  such  an  instrument,  suspend  it  in  a  clamp 
from  a  stand  over  the  heart.  By  two  stitches  made  with  a 
needle  in  the  upper  and  lower  ends  of  the  left  ventricle 


RECORDING  HEART  TRACINGS 


151 


fasten  the  lower  ends  of  the  two  levers  firmly  to  the  heart. 
As  the  ventricle  beats  air  will  be  forced  in  and  out  of  the 
tambour  on  the  apparatus.  With  rubber  tubing  connect 
the  apparatus  to  a  medium  sized  tambour  which  records  be- 
low the  blood-pressure  on  the  drum.  Cushny  has  devised 
a  myocardiograph  which  may  be  used  to  advantage.  (Eber- 
bach  and  Son  Company,  Ann  Arbor,  Mich.)  With  this  in- 
strument the  drum  must  be  brought  to  the  side  of  the 
animal.    (See  Fig.  317.) 

If  no  special  apparatus  is  available,  then  a  pin  hook  can 


i— To  tdmbour 


Thistle  tube 


Cardiomefer 

Elastic  rubber 
dam 


Fig.  143. — Cardiometer  made  from  a  large  thistle  tube.  A  hollow  rubber  ball  with 
an  opening  cut  in  one  side  and  a  tube  in  the  other  may  be  made  into  a  cardiometer 
by  cementing  a  perforated   rubber  membrane  over   the   opening  in   the   side   of   the   ball. 

be  attached  to  the  heart.  A  string  is  tied  to  the  pin  and 
passed  over  pulleys  to  an  ordinary  (weighted)  frog  heart 
lever  which  writes  on  the  drum.  Or  a  rubber  membrane 
(in  the  center  of  which  a  screw  is  attached,  see  Fig.  374)  is 
tied  over  a  cardiometer  (Fig.  142)  and  the  string  attached 
to  the  heart  by  the  pin  hook  is  fastened  to  the  screw  in  the 
membrane.  The  cardiometer  is  held  in  a  clamp  and  con- 
nected Avith  a  recording  tambour.  Another  method  of  re- 
cording heart  tracings  is  shown  in  Fig.  1 44. 

When  all  adjustments  are  made  place  adrenaline  solu- 


152 


EXPERIMENTAL   PHARMACOLOGY 


tion  in  one  burette  and  thirty  per  cent  alcohol  in  the  other. 
Start  the  drum  with  a  medium  speed  and  take  a  short  nor- 
mal record.  If  everything  is  satisfactory  then  inject  two 
cubic  centimeters  of  alcohol  if  the  animal  is  a  dog,  or  one- 
half  cubic  centimeter  if  vou  have  a  cat.    From  the  results 


Fig.  144. — Arrangement  of  apparatus  for  recording  the  movements  of  one  auricle 
and  one  ventricle.  The  heart  is  held  in  a  special  holder  (Fig.  145)  here  but  sometimes 
the  pericardium  is  slit  open  and  the  edges  are  stitched  to  the  sides  of  the  chest  so  that 
the  heart  lies  in  a  sort  of  hammock. 

of  this  first  dose  you  can  estimate  about  what  sized  doses 
the  animal  mil  be  able  to  overcome  later.  This  will  vary 
with  each  experiment  and  the  student  should  early  learn 
to  estimate  doses  of  drugs  of  Ioav  toxicity.    With  very  pois- 


CARDIOGRAPHIC  TRACINGS 


onous  drugs  the  dose  must  be  given  much  more  accurately. 
How  does  this  first  dose  affect  the  heart  tracing?  Increase 
the  dose  and  secure  marked  effects  from  the  heart.  Ob- 
serve the  appearance  of  the  organ  while  the  drug  is  acting. 
The  respiratory  movements  of  the  lungs  may  disturb  your 
cardiac  apparatus  and  show  notches  at  the  top  and  bottom 
of  your  heart  tracing.  To  check  this  reduce  the  respira- 
tory movements  as  much  as  possible  by  shutting  down  the 
amount  of  air  blown  into  the  lungs.    Note  carefully  any 


Right  bowl 


Fig.    145. — Special    heart    holder    to    keep    the    heart    from    moving    with    the    lungs    as 
they  contract  and  expand  from  the   artificial   respiration. 


effect  this  may  have  on  blood-pressure.  Watch  your 
anesthesia  carefully  and  do  not  give  too  much  ether.  Make 
one  injection  (i^  c.c.  for  a  dog,  14C.C.  for  a  cat)  of  adrena- 
line and  obtain  a  tracing  showing  the  action  of  this  drug 
on  the  heart. 

2.  Now  obtain  tracings  showing  the  action  of  whiskey, 
brandy  and  "wine.  Can  you  use  beer  or  champagne  for  in- 
travenous injections'?  On  what  do  you  base  your  conclu- 
sions?    Record   the  rectal   temperature   again   and   com- 


154 


EXPERIMENTAL    PHARMACOLOGY 


Fig.  146. — Heart  levers  for  dogs.  The  writing  lever  is  made  of  heavy  aluminum 
wire  which  is  coiled  around  a  small  wire  nail  to  form  the  hinge.  The  nail  is  driven 
tightly  into  a  small   hole   drilled   in   the   end   of   a   3/16   inch   brass    rod. 


Medulla 

oblongata 

N.Xt 
Cervical  1 

Accessory  n.- 
H)  trapezius/ 


Spinal 
medulla- 
(cord) 


Rami 

communican- 
tes  going  to 
Symp.  gang, 
(preganglionic) 
Ansa 

subciavia 
[Annulus  of 
Vieussens)?" 

ThoracicLs 
nerves 


Postgdnglionic  fibers 

dre  clotted  thus 


Inferior 
cervical 
gan 


Jugular  ganglion  (Gang,  of  the  root) 
Depressor  (Fall  in  pressure  or  slowing  of  heart.) 
(Sensory)    Separate  nerve  in  rabbit  and  opossum. 

Nodosum  ganglion  (Gang,  of  the  trunk)      Hatrinqton) 
Inhibitory  cranial  autonomic  fibers 

Superior  cervical  ganglion 
-Descending  sympathetic  fibers  in  cord 
^Cervical  vd  go -sympathetic  trunk 


^Electrodes    (slowing  or  stoppage  of 
Subclavian       heart  Augmentation  in  some 
art     ^  ^ — t;^  animals.) 

Aortic  arch 


first  thoracic  ganglion 
(5tell3te) 


Electrodes 
(Acceleration,  or 

augmentation  of  heart.) 


Fig.    147. — Schematic   representation   of  the   innervation  of   the   heart. 


SYMPATHETIC    CARDIAC    NERVES 


155 


pare  this  reading  with  the  former  one.    What  conclusions 
can  you  draw? 

3.  If  the  animal  is  in  fair  condition,  isolate  the  right 
subclavian  vein  at  the  apex  of  the  chest  (see  Figs.  133  and 
184).  Tie  tightly  two  ligatures  around  the  vein  and  sec- 
tion the  vessel  between  the  ligatures.  Pick  up  the  ansa 
subclavia  (annulus  Vieussenii)  and  stimulate  some  of  the 


Depressor  nerve 
{running  with 
the  vagus  trunk 
on  the  right) 


Union  between 
middle  cervical 
ganglion  and 
vagus  nerve 

Fibers  from 
spinal  cord 
to  stellate 
ganglion 

Right 
stellate 
{ inf.  cervical) 
ganglion 


Communica 
branches  bet}^een 
the  vagus  and  the 
stellate  ganglion 


Union  between 
middle  cervical 
ganglion  and 
vagus  nerve 


Left  stellate 
inf.  cervical) 
"ganglion 

Fibers  from 
spinal  cord  to 
stellate  gang. 

Depressor  nerve 

-Cardiac  nerves 

from  the 
stellate  ganglion 


Fig.    148. — The   innervation   of   the   heart   in  the   cat.      (After   Boehni.) 


small  fibers  passing  from  the  ganglia  or  the  anterior  loop 
of  the  annulus  toward  the  heart.  These  will  probably  be 
derived  from  the  vagus  and  the  heart  will  then  be  slowed. 
Pick  up  some  others  of  the  small  fibers  lower  doA\ai  and 
stimulate  them.  You  will  probably  find  a  fiber  which  does 
not  cause  any  slowing  of  the  heart  and  no  immediate  effect 
may  follow  its  stimulation.  But  if  you  get  a  pure  sympa- 
thetic cardiac  fiber,  stimulation  of  this  nerve  will,  after  a 


156 


EXPERIMENTAL   PHARMACOLOGY 


AiSTTISEPTIC  ACTION   OF  ALCOPIOL 


157 


i^ery  perceptible  latent  period,  cause  a  change  in  the  heart 
beat  either  producing  an  acceleration  of  the  rate  or  in- 
creasing the  strength  of  the  beat  (augmentor  effect).  If 
possible,  secure  tracings  showing  these  effects  on  the  heart. 
How  do  these  records  compare  with  the  action  of  adrena- 
line on  the  heart?  Do  you  know  of  any  other  drugs  that 
act  on  the  heart  similarly  to  adrenaline?  Watch  for  these 
later  in  your  course.    Kill  the  animal  \)j  asphyxia. 


EXPEEIMENT  XY. 
Antiseptic  Action  of  Alcohol. 

1.  Obtain  four  fermentation  tubes  (Fig.  150).     Place  a 
cake  of  yeast  in  two  hundred  cubic  centimeters  of  water, 


Fig.    150. — Fermentation    tube. 


add  some  glucose  and  shake  up  the  mixture  thoroughly. 
Pour  out  enough  of  the  mixture  to  fill  one  fermentation 
tube,  add  sufficient  absolute  alcohol  to  the  mixture  to  make 


158  EXPERIMEISTTAL    PHARMACOLOGY 

a  one  per  cent  solution  and  fill  the  tube.  Similarly  till  the 
other  three  tubes  with  the  mixture,  but  place  in  the  second 
tube  ten  per  cent  of  alcohol,  in  the  third,  forty  per  cent, 
and  in  the  fourth,  seventy  per  cent.  Be  sure  the  air  is  all 
out  of  the  tops  of  the  tubes.  Place  these  in  an  incubator 
at  37  degrees  Centigrade  (or  in  a  warm  room)  until  the 
next  day.  Then  examine  the  tubes  and  record  any  obser- 
vations you  may  make.  A  culture  of  colon  bacilli  may  be 
used  instead  of  yeast. 

EXPERIMENT  XVI. 

Alcohol,  Brandy,  Urethane,  Chloral.   (Dog:  Blood-pressure, 
Respiration,  Cerebrospinal  Fluid,  Kidney  or  Spleen.) 

1.  Etherize  a  dog  and  arrange  for  blood-pressure  and 
respiratory  tracings.  Provide  two  injecting  burettes  (one 
containing  adrenaline,  the  other  twenty  per  cent  alcohol). 
Turn  the  dog's  head  to  the  left,  trephine  the  skull  (see 
Figs.  97  and  100;  also  read  Experiment  V,  2,  page  103). 
Make  the  trephine  opening  in  the  skull  as  carefully  as  pos- 
sible so  the  edges  will  be  smooth  and  regular.  With  small 
scissors  cut  away  the  dura  mater  over  the  area  covered 
by  the  opening.  Do  not  injure  the  brain  and  try  to  avoid 
all  hemorrhage.  Now  place  a  perforated  (rubber)  cork 
tightly  in  the  opening  so  that  solutions  cannot  leak  around 
it.  The  corh  must  not  press  on  the  brain.  The  perfora- 
tion in  the  cork  carries  a  small  (5/16  inch)  glass  tube. 
This  tube  is  filled  with  salt  solution  and  then  connected 
by  rubber  tubing  to  a  small  water  manometer  (Fig.  151). 
From  the  funnel  the  manometer  and  tubing  are  filled  with 
normal  salt  solution,  the  glass  tube  in  the  cork  is  filled 
with  salt  solution  from  a  pipette,  and  the  rubber  tube  is 
slipped  over  the  glass  tube.  This  makes  a  complete  fluid 
connection  between  the  cerebrospinal  fluid  in  the  subdural 
spaces  and  the  meniscus  of  the  salt  solution  in  the  left 
hand  limb  of  the  manometer.     For  adjustments  in  pres- 


EECORDING  CEREBROSPIlsTAL  PRESSURE 


159 


sure,  the  manometer  can  be  moved  up  and  down  on  the 
stand.  The  dog's  head  can  now  be  rotated  back  to  the 
original  position  and  the  pin  put  through  between  the 
teeth.  Mark  on  the  glass  (or  record  from  the  scale)  the 
level  of  the  meniscus. 

Adjust  the  apparatus  to  record  blood-pressure  and  res- 
piration. If  you  have  a  small  and  very  sensitive  tambour 
you  may  also  connect  this  to  the  top  of  the  manometer  tube 


Fig.   151. — Arrangement  of  apparatus  for  recording  the  pressure  of  the  cerebrospinal  fluid. 


(left)  and  try  to  record  changes  in  the  pressure  of  the 
cerebrospinal  fluid.  Othermse  simply  observe  and  write 
do^^^l  the  variations  which  the  manometer  shows.  Becht  at 
the  University  of  Chicago  records  intracranial  pressure 
by  means  of  a  long  glass  tube  inclined  upward  at  a  slight 
angle  from  the  horizontal.  In  this  way  a  slight  increase  in 
pressure  moves  the  fluid  in  the  small  bore  of  the  glass 
tube. 


160 


EXPERIMENTAL   PHARMACOLOGY 


2.  With  a  medium  tetanizing  current  stimulate  the  right 
vagus  nerve  for  a  second  or  so.  How  does  this  affect  the 
respiration,  blood-pressure,  and  cerebrospinal  pressure? 
What  mechanical  factors  are  involved!  Now  inject  one- 
half  cubic  centimeter  of  adrenaline  and  repeat  3^our  obser- 
vations.   What  mechanical  factors  are  concerned? 

When  the  records  return  to  normal  inject  two  cubic  cen- 


Fig.    152. — Spleen   oncometer    for    dogs.      A   little   less   than   natural   size. 

timeters  of  alcohol.  Note  the  effect  on  the  circulation  and 
respiration  and  then  estimate  how  much  larger  dose  you 
can  safely  inject.  When  the  records  return  to  the  nor- 
mal inject  more  alcohol  and  watch  carefully  for  changes  in 
the  cerebrospinal  fluid.  It  may  be  necessary  to  inject  three 
or  four  times  to  produce  any  results.  What  do  3^ou  ob- 
serve? How  do  you  explain  this?  Stop  the  drum  and 
wait  ten  minutes  to  allow  the  animal  to  recover  and  to  see 


ADJUSTMENT    OF    ONCOMETER 


161 


if  other  changes  occur  in  the  pressure  of  the  cerebrospinal 
fluid.  The  anesthesia  should  be  as  nearly  perfect  as  pos- 
sible while  the  above  parts  of  the  experiment  are  being 
performed. 

3.  With  a  median  longitudinal  incision  now  open  the 
abdomen  and  place  hemostats  at  each  side  on  the  edges  of 
the  wound.  Pull  upward  and  outward  on  these  (two)  hem.- 
ostats  and  expose  the  viscera.  Bo  not  manipulate  these 
organs  any  more  than  you  can  help  or  the  animal  may  pass 
into  a  condition  of  shoch.  Keep  the  intestines  inside  the 
abdomen.  If  you  have  a  spleen  oncometer  (Figs.  152  and 
153)  this  is  easiest  for  a  beginner  to  adjust.     Gently  pull 


Fig.    153. — Spleen   oncometer  for  dogs.     About   one-half   natural  size. 


the  spleen  forward  and  fit  it  into  the  oncometer,  close  the 
instrument  and  place  it  back  into  the  abdomen,  attach  the 
tube  for  the  tambour  and  close  the  abdomen  air  tight  with 
three  or  four  hemostats.  (Sew  it  up  if  you  do  not  have 
hemostats.)  The  abdominal  ivoiind  must  be  closed  tightly 
and  there  should  be  no  internal  hemorrhage.  If  you  have 
a  kidney  oncometer  (Figs.  154  and  156)  instead  of  one  for 
the  spleen,  then  refer  to  Fig.  158,  and  in  the  manner  there 
sho^^^l  expose  the  left  kidne^^  Do  not  injure  the  renal  ves- 
sels but  gently  lift  up  the  kidne}'  and  slip  it  into  the  on- 
<?ometer.  Carefully  avoid  catching  loops  of  the  intestines 
or  a  piece  of  the  omentum  in  the  oncometer.  Close  the  lid 
and  fasten  the  latches  (or  put  on  the  rubber  band)  and 
connect  the  tube  for  the  tambour.     Carefully  replace  the 


162 


EXPERIMENTAL   PHAEMACOLOGY 


Fig.    154. — Kidney   oncometer   (natural   size   for  medium  sized   dogs).      Front   view.      Made 

of   sheet   brass. 


Fig.    155. — Rear   view    of    same    oncometer   shown    in    Fig.    154. 


ONCOMETERS 


163 


I'ig.   156. — Front   view  of  kidney   oncometer  made  of  a  round   metal  pill   or   ointment  box. 
Closed   by   a  rubber   band. 


l'"ig.    157. — View   showing  the   oncometer   partly   open.      This    oncometer    can   also    be    used 
well  for  a  loop  of  the  intestine. 


164 


EXPERIMENTAL   PHARMACOLOGY 


intestines  around  the  kidney    and    close    the    abdominal 
wound  tightly. 

The  recording  tambour  should  have  a  fairly  large  bowl 
and  the  magnification  should  be  large.    Adjust  all  writing 


Fig.  158. — Dissection  showing  tlie  method  of  exposing  the  kidney  from  a  median 
incision.  Do  not  cut  across  the  side  of  the  abdominal  wall.  When  the  kidney  is  placed 
inside  tlie  oncometer  the  abdomen  is  closed  air  tight  with  hemostats.  LK,  left  kidney. 
S,   stomach.     RA,   renal   artery.     ixV ,   renal   vein.      U,   ureter.     1,  intestine. 


ADJUSTMENT  OF  APPARATUS 


165 


points  on  the  drum,  recording  from  above  downward,  on- 
cometer, blood-pressure,  respiration,  base  line  and  time 
signal.  The  ivriting  'points  should  not  he  in  a  straight  line 
perpendicularly  hut  should  he  so  adjusted  that  each  tivo 
adjacent  pointers  can  just  pass  each  other. 


^rom  pressure  bottle 


Spleei 


Fig.  159. — Arrangement  of  apparatus  for  making  several  records  at  the  same  time 
on  the  drum.  The  proper  adjustment  of  these  tambours,  etc.,  is  one  of  the  most  dif- 
ficult parts  of  the  whole  experiment.  Suitable  stands  which  can  be  placed  close  to- 
gether  at   the   bottom   aid  greatly.      (See   chapter    on   shop    work.) 

4.  Start  the  drum  and  inject  one-half  cubic  centimeter 
of  adrenaline.  Make  a  small  cross  just  under  the  position 
of  each  record  at  the  moment  of  injecting  the  drug.  Do 
you  get  a  satisfactory  record?  The  purpose  of  this  in- 
jection is  to  show  you  what  a  good  spleen  or  kidney  volume 
tracing  should  look  like. 

Consult  the  instructor  to  get  his  opinion  of  your  record. 


166  EXPERIMENTAL   PHAEMACOLOGY 

Now  stimulate  one  vagus  nerve  and  record  the  result. 
A^Hien  all  the  pointers  return  to  normal  inject  a  fair  sized 
dose  of  alcohol.  Does  this  affect  the  blood-pressure?  How 
does  the  spleen  or  kidney  tracing  obtained  now  compare 
with  the  one  produced  by  adrenaline  ?  How  do  you  explain 
this?  What  mechanical  factors  are  involved?  Inject  an- 
other dose  of  adrenaline  and  see  if  you  can  determine  two 
phases  to  the  adrenaline  action.  How  do  you  explain  this? 
Now  obtain  tracings  showing  the  action  of  brandy,  ure- 
thane  (ten  per  cent  solution,  two  cubic  centimeters  for  the 
first  injection),  and  chloral  (four  per  cent  solution,  one 
cubic  centimeter  for  the  first  injection).  The  oncometer 
tracing  is  liable  to  become  unsatisfactory  after  three  or 
four  records  have  been  obtained  from  it.  Can  you  deter- 
mine what  this  is  due  to?  (See  Fig.  160.)  How  do  ure- 
thane  and  chloral  affect  the  blood-pressure  and  respira- 
tion? Which  is  the  more  active  drug?  Kill  the  animal 
by  closing  off  the  respiration.  Do  you  get  an  oncometer 
tracing?    How  is  the  blood-pressure  affected? 

5.  If  time  permits,  carry  out  the  following  dissections : 
Open  the  chest  by  a  median  longitudinal  incision  and  pull 
the  heart  (pericardium)  over  to  the  right  side.  Deep  down 
in  the  chest  (behind  the  diaphragm  as  it  arches  upward) 
and  a  little  way  latterly  from  the  median  line  you  will  find 
the  esophagus  and  the  aorta.  These  can  be  traced  down 
from  the  upper  part  of  the  chest  and  from  the  heart.  Look 
for  the  vagus  trunks  on  the  esophagus  (Fig.  161).  Be- 
neath the  pleura  at  the  side  of  the  spinal  column  you  can 
find  the  main  branches  of  the  thoracic  sympathetic.  Pick 
these  up  and  trace  them  do\^al  behind  the  diaphragm. 
Open  the  abdomen,  divide  the  diaphragm,  and  pull  the 
stomach  and  liver  to  the  right.  Can  you  trace  the  passage 
of  these  sympathetic  fibers  from  the  chest  down  into  the 
abdomen?  Observe  carefully  the  exact  position  which  the 
fibers  occupy  and  see  into  what  kind  of  a  structure  thev 
pass.    If  the  stomach,  liver  and  diaphragm  were  in  their 


\ 


V. 


Fig.  160. — Illustration  showing  the  appearance  of  the  blood-vessels  in  the  ears  of  a 
white  rabbit.  (By  permission  of  Seelig  and  Joseph.)  "To  show  the  contrast  between  the 
constricted  vessels  still  connected  with  the  vaso-constrictor  center  (left  ear)  and  the  control 
dilated  vessels  that  have  been  disconnected  from  that  center  (right  ear).  Drawing  made 
late  in  the  e.xperiment  when  the  animal  was  apparently  in  a  state  of  deep  shock.  The  strong 
vaso-constriction  in  the  left  ear  was  replaced  by  a  wide  dilatation  as  soon  as  the  connection 
of  this  ear  with  the  vasomotor  center  was  severed."  (From  Seelig  and  Joseph:  Jour,  of 
Laboratory  and  Clinical  Medicine,  1916,  i,  p.  283.)  This  illustration  shows  the  continued 
marked  activity  of  the  vaso-constrictor  center  in  the  ears  of  animals  when  they  are  apparently 
"in  a  state  of  deep  shock."  The  student  is  urged  to  be  constantly  on  the  watch  to  see  if 
he  can  observe  a  similar  action  of  the  center  on  the  vessels  of  the  kidney,  spleen  or  intestinal 
loop  as  indicated  by  the  character  of  the  oncometer  records  in  animals  which  do  well  in  the 
early  part  of  an  experiment  but  pass  apparently  into  "a  state  of  deep  shock"  in  the  later 
stages  of  the   experiment.     In  this  case   how   would   the   oncometer   records   be  affected? 


Fig.  161. — Dissection  (dog)  showing  the  position  of  the  left  pulmonary  vessels  and  the 
sympathetic  trunk  in  the  chest  above  the  diaphragm.  Ms,  mediastinum;  il/c',  mammary 
vessels  (seen  through  the  mediastinal  membranes);  T,  thymus;  /',  vagus  trunk;  Pa,  left 
pulmonary  artery;  Pts,  left  pulmonary  veins;  H,  heart  covered  over  by  the  pericardium. 
The  connection  of  the  pericardial  sac  to  the  diaphragm  is  torn  loose  from  the  diaphragm 
at  the  edge,  P;  Pli,  left  phrenic  nerve  lying  on  the  pericardium;  Ln,  lower  lobe  of  the 
left  lung;  V,  V,  branches  of  the  vagus  trunks  on  the  esophagus,  Oe;  Ao,  aorta;  Sy,  sym- 
pathetic trunk;   D,   D,  diaphragm;   Lv,   liver;   5',   edge   of   stomach. 


PRACTICE   DISSECTIOlv'S 


167 


normal  position,  could  you  now  find  these  same  fibers  in 
the  abdomen?  Consult  Figs.  158  and  162.  Perform  a 
similar  dissection  on  the  right  side.    Could  you  find  these 


Fig.  162. — Dissection  to  show  the  abdominal  viscera  (dog).  I,  intestin^;  O,  omen- 
tum; D,  duodenum;  P,  pancreas;  Sp,  spleen;  Lv,  liver;  S,  stomach;  RK,  right  kidney; 
LK,  left  kidney;  LO,  left  ovary;  RO,  right  ovary;  RU,  right  ureter;  LU ,  left  ureter; 
RH .  right  uterine  horn;  LH,  left  uterine  horn;  U,  uterus;  R,  rectum;  B,  bladder  (pulled 
outward  and  downward). 


fibers  and  stimulate  them  electrically  in  a  living  animal? 
On  which  side  are  the  fibers  easier  to  reach  ?  AAHiat  are  the 
functions  of  the  splanchnic  nerves?  Consult  Fig.  318  to 
determine  the  s'eneral  distribution  of  the  visceral  nerve. 


168  EXPERIMEiSTTAL   PHARMACOLOGY 

EXPERIMENT  XVII. 

Chloral  Hydrate,  Urethane,  Paraldehyde,  Chloretone. 
(Frogs:  Central  Nervous  System.) 

1.  Into  the  anterior  lymph  sac  (Fig.  66)  of  a  frog  in- 
ject (see  Figs.  125  and  126)  one  cubic  centimeter  of  fonr 
per  cent  chloral  hydrate  solution.  Place  the  frog  on 
moist  cotton  in  a  battery  jar  and  observe  its  s^anptoms. 
Try  its  reflexes  from  time  to  time  by  touching  it.  Turn 
it  over  and  see  if  it  can  regain  its  normal  position.  Are 
there  any  s^n^nptoms  of  stimulation?  Some  local  irritation 
may  be  caused  by  the  drug  when  first  injected.  How  long 
does  it  take  for  the  animal  to  become  completely  narco- 
tized? How  do  the  synijotoms  compare  with  those  pro- 
duced by  ether,  chloroform  or  nitrous  oxide  f 

2.  Into  the  anterior  Ij-mph  sac  of  another  frog  inject  one 
cubic  centimeter  of  a  ten  per  cent  urethane  solution.  Care- 
fully observe  its  symptoms,  noting  the  condition  of  the 
reflexes,  power  of  equilibrium,  etc.,  from  time  to  tiniie. 
How  does  this  drug  compare  mth  chloral  or  ether? 

3.  Inject  another  frog  Avith  one-half  cubic  centimeter  of 
paraldehyde.  Observe  its  actions  carefully  and  compare 
these  mth  those  manifested  b}^^  the  other  frogs.  What 
structures  or  organs  are  chiefly  concerned  in  the  produc- 
tion of  the  symptoms  you  observe?  How  would  a  decere- 
brated frog  act  under  paraldehyde? 

4.  Inject  a  fourth  frog  with  chloretone  solution.  This 
solution  can  be  made  up  as  follows :  Place  about  half  a 
gram  of  chloretone  crystals  in  a  beaker  and  pour  a  few 
drops  of  absolute  alcohol  over  the  drug.  The  chloretone 
should  soon  dissolve.  Now  add  water  until  faint  traces  of 
a  precipitate  (white)  begin  to  appear.  Then  add  just 
enough  alcohol  to  redissolve  the  preciiDitate.  Of  this  solu- 
tion one  or  two  cubic  centimeters  may  be  injected  into  the 
frog.  (Chloretone  is  also  sometimes  dissolved  in  olive  oil 
for  administration  to  animals.) 


ACTION   OF   CHLORAL  HYDEATE  169 

Save  all  the  frogs  until  next  day  and  note  all  later  symp- 
toms. How  does  the  length  of  duration  of  the  anesthesia 
compare  with  that  produced  by  ether  or  chloroform?  Do 
any  of  the  frogs  recover?  If  not,  smaller  doses  may  be 
tried  again. 

EXPERIMENT  XVIII. 
Chloral  Hydrate.    (Action  on  the  Frog's  Heart.) 

1.  Pith  a  frog  and  arrange  for  recording  heart  tracings 
(see  Fig.  63).  Obtain  one  or  two  normal  tracings  (show- 
ing the  effect  of  vagus  stimulation)!  Start  a  new  round  on 
the  drum  and  apply  four  per  cent  chloral  hydrate  solu- 
tion to  the  heart  with  a  medicine  dropper.  Stimulate  the 
vagus  nerve  from  time  to  time  and  note  any  changes.  Con- 
tinue the  application  of  the  drug  until  the  heart  stops. 
Time  the  record  and  draw  three  or  four  horizontal  com- 
parison lines  around  the  drum  between  the  records.  These 
lines  are  made  by  rotating  the  drum  b^^  hand  while  a  sta- 
tionary^ tambour  pointer  or  signal  magnet  pointer  marks 
on  the  drum.  How  did  the  drug  affect  the  tonus  of  the 
heart  muscle?  Was  the  inhibitory  apparatus  affected? 
Examine  the  condition  of  the  auricles  and  ventricle. 

EXPERIMENT  XIX. 

Chloral  Hydrate.     (Frog:  Retinal  Circulation  With  the 
Ophthalmoscope.) 

1.  Examine  carefully  an  ophtlialmoscope  (Fig.  163). 
Fasten  a  frog  to  a  board  as  shown  in  Fig.  164.  Then  Avith 
the  ophthalmoscope  look  into  the  frog's  eye  from  a  posi- 
tion in  front  of  the  animal,  but  slightly  from  above  and 
from  the  side.  Turn  the  lenses  in  the  instrument  until  you 
find  one  that  permits  you  to  see  the  red  blood  vessels  in 
the  fundus  of  the  eve.    Examine  these  carefullv.     Can  vou 


170  EXPEKIMENTAL   PHAEMACOLOGY 

detect  any  movement  inside  these  vessels!  The  larger 
ones  show  a  motion  resembling  that  of  a  rapidly  moving 
belt.  Seek  out  some  very  fine  vessels  and  watch  for  move- 
ments of  the  corpuscles.  Can  you  distinguish  individual 
corpuscles  in  these  finer  vessels?     Find  a  place  where  a 


Fig.    163. — Klectric   ophthalmoscope.      The   small    (replaceable)    battery   is   concealed   in  the 
handle   of   the   instrument. 

very  small  vessel  divides.  Watch  the  movements  of  the 
corpuscles  as  they  strike  against  the  walls  of  the  vessel  at 
the  point  of  division.  Can  you  see  this  in  the  human  eye! 
Now  carefully  observe  the  rate  and  appearance  of  the 
corpuscle  flow  in  some  easily  observed  (very  small)  ves- 


RETINAL  CIRCULATION   CHANGES 


171 


sels.     Keep  this  observation  carefully  in  mind  for  later 
comparisons. 

Under  the  skin  of  the  back  inject  with  a  hypodermic  syr- 
inge one  cubic  centimeter  of  four  per  cent  chloral  hydrate 
solution.  At  intervals  of  five  minutes  or  less  again  care- 
fully observe  the  rate  and  appearance  of  the  corpuscle  flow 
in  the  vessels  previously  examined.  Does  the  frog  become 
deeply  narcotized?     How  does  chloral  affect  the  heart? 


Fig.  164. — Position  and  method  used  for  observing  the  retinal  circulation  in  a  frog. 
The  ophthalmoscope  shown  in  Fig.  163  is  being  used,  but  several  other  (cheaper)  forms 
of   ophthalmoscopes   are    on    the   market    and   may    be    equally   well   employed. 

Are  the  muscular  walls  of  the  vessels  directly  affected  by 
chloral  hydrate?  What  conclusions  can  you  draw  from 
this  experiment? 

You  may  repeat  this  experiment  using  urethane  or 
paraldeh^^de  or  chloroform  to  anesthetize  the  frog  if  you 
have  time.  Later  in  your  course  other  drugs,  such  as  nitro- 
glycerine, amylnitrite,  arecoline,  atropine,  etc.,  may  also 
be  used  in  this  experiment. 


172  EXPERIMENTAL   PHARMACOLOGY 

EXPEEIMENT  XX. 

Chloral  Hydrate,  Adrenaline.    (Turtle's  Heart.) 

1.  Pith  a  turtle  and  take  a  normal  heart  tracing.  Then 
drop  on  the  heart  four  per  cent  chloral  hydrate  solution 
until  the  beats  become  slow.  Then  drop  on  adrenaline 
solution  (1:10,000)  and  note  carefully  any  change  in  rate 
or  amplitude  of  the  heart  record.  T\niat  structures  are  af- 
fected by  each  drug?  "What  conclusions  can  you  draw 
from  the  experiment? 

EXPERIMENT  XXI. 

Chloral  Hydrate  and  Alkalies. 

1.  Into  a  test  tube  containing  two  cubic  centimeters  of 
a  four  per  cent  chloral  hydrate  solution  pour  an  equal 
volume  of  potassium  hydrate  solution.  AVhat  do  you  ob- 
serve ?  Smell  the  mixture.  What  do  you  note  1  A  reaction 
represented  by  the  following  equation  has  taken  place : 

CCI3CHO  4-  KOH  =  CHCI3  +  HCOOK 

What  bodies  are  formed?    Are  they  soluble  in  water? 

EXPERIMENT  XXII. 
Morphine.     (Frog:  Central  Nervous  System.) 

1.  Into  the  anterior  lymph  sac  of  a  frog  inject  one  cubic 
centimeter  of  four  per  cent  morphine  acetate  solution. 
(The  sulphate  or  hydrochlorate  of  morphine  may  be  used 
instead.)  Place  the  animal  on  moist  cotton  in  a  battery 
jar  and  observe  its  actions.  Try  the  reflexes  from  time 
to  time.  Are  the  pupils  affected?  Is  there  any  change  in 
the  respiratory  movements?  How  does  the  action  of  the 
drug  compare  with  that  of  nitrous  oxide  or  chloral?  If 
the  frog  becomes  completely  narcotized  do  not  cast  it  aside 


ACTIOX    OF    OPIUM   ALKALOIDS 


173 


Lilt  carefully  save  it  until  the  next  day  observing  it  several 
times  in  the  meantime  if  possible.  Do  you  note  any 
changes  in  the  reflexes  at  any  time?  Does  the  frog  re- 
cover! What  symptoms  are  exhibited  during  the  recover}^ 
2Deriod?    How  do  3^ou  explain  this? 

EXPERIMENT  XXIII. 

Thebaine,  Codeine.    (Frog:  Central  Nervous  System.) 

Inject  a  frog  with  one  cubic  centimeter  of  two  per  cent 
thebaine  solution  and  a  second  animal  with  one  cubic  centi- 
meter of  two  per  cent  codeine  solution.  Place  the  frogs  on 
moist  cotton  in  a  battery  jar  and  watch  the  s^nnptoms  pro- 
duced by  the  drugs.  Compare  these  animals  with  the  one 
that  got  morphine. 

.     EXPEPtlMENT  XXIV. 

Morphine.    (Chemical  Test  for  Morphine.) 

1.  Add  a  few  droi3S  of  a  dilute  mixture  of  ferric  chloride 
and  potassium  ferricyanide  solutions  to  a  morphine  salt  so- 


0/factory  nerves 
Olfactory  lobe  — 


tIallGck- 


CerebrdI  hemisphere 

Optic  trdct 
Hypophysis 

Ni.  Optic  lobe 
N.v  Cerebellum 
MedullQ  oblongdtd 


Spinal  cord 


Fig.    165. — Ventral   and   dorsal  views  of   a   pigeon's  brain.      (^Modified   from   Wiedersheim.) 


174 


EXPERIMENTAL   PHAEMACOLOGY 


lution.     A  deep  blue  color  appears.     Considerable  mor-- 
phine  produces  a  precipitate  of  Prussian  blue. 

Potassium  ferricyanide  oxidizes  morphine  to  oxy-dimor- 
phine : 

2  C„B;,N03  +  2  KOH  +  K,re,(CN),,  =  2H,0  +  (C„H,,N03),  +  2K,Fe  (CN), 
MorpMne  Potassium  Oxy-dimorphine     Potassium 

ferricyanide  ferrocyanide 

Potassium  ferrocyanide  then  forms  Prussian  blue  with 


Cerebrum 


Optic  lobe 
Cerebellum 


Semicircular 
Canals 
Medulla  oblongata 


Spinal  cord 


Fig.    166. — Posterior  view   of   the   brain   and  semicircular   canals   of   a   pigeon. 


SKin  (cut) 


Cut  edge  of  skull  bone 
Cerebrum 


Optic  lobe 
Cerebellum 


.Semicircular 
canals 

Medulla 


spinal 
cord 


-f^rf/ec^- 


Fig.    167. — L,ateral    view    of    the    head    of    a   pigeon    showing   the   brain,    external    auditory 
opening   and    semicircular   canals. 


GENERAL  ACTION   OF    MORPHINE 


175 


ferric  chloride  (Autenrieth  and  Warren).  The  instructor 
may  give  you  other  tests  for  morphine  if  he  desires  to 
do  so. 


EXPERIMENT  XXV. 

Morphine.     (Dog:    Respiration,  Excretion,  Pupils,  Central 
Nervous  System,  General  Symptoms.) 

1.  Inject  subcutaneously  into  a  dog  twenty  milligrams 
(one  cubic  centimeter  of  two  per  cent  solution)  per  kilo- 


Olfacfory  bulb 


Optic  nerve 


Optic  chiaswa 
Opiic  frdcf 


Hypophy. 


Cerebral 
peduncle 

Pons  - 


Facial  nerve 
Acoustic  nerve 


Olfactory  trad 
Sulcus  rhinalis 

■  -  Fossa  lateralis 


Piriform  lobe 
-Oculomoior  verve 

Trochlear  nerve 


Triqeminal  nerve 


^'^r^i  -  -al'l'^.^^  Abducent  nerve 
1 1  ---'~\~^^^0''P^^  frapezoideum 
^Si.-'"    ■    I     --^'^^-m--  Olosso-pharynqeal nerve 
^r^*^     '/    '    .    4^^\^~  -'^aqus  nerve 
Pyramid^''  ^^^^  J        '-0^^--  Accessory  nerve 

Spinal  cord  --'  't\/H 


^\   - 


'ian  fissure 


Fig.    168. — Base   of    the    brain    of   a    dog.      (Modified    from    Sisson.) 

gram  of  weight  of  morphine  hydrochlorate  (or  the  acetate 
or  sulphate).     Note  carefully  the  size  of  the  pupils  and 


176  EXPERIMENTAL   PHARMACOLOGY 

watch  for  any  change  in  these.  Allow  the  animal  to  walk 
about  the  room  and  do  not  disturb  it  at  first.  How  is  the 
respiration  affected?  Does  the  animal  vomit?  If  so,  can 
you  detect  morphine  in  the  vomitus  ?  How  is  morphine  ex- 
creted? Is  there  present  an  increase  in  the  secretion  of 
saliva?  How  do  you  account  for  this?  Does  the  animal 
defecate?  How  is  the  intelligence  of  the  dog.  affected? 
What  later  changes  do  you  note  in  the  respiration?  Are 
there  any  symptoms  of  excitement?  Take  the  rectal  tem- 
perature. When  the  animal  lies  down  and  becomes  quiet, 
then  try  its  reflexes  from  time  to  time  by  pinching,  loud 
noises,  etc.  Eecord  the  respiration  on  the  drum  and  watch 
for  irregularities  (Che^me-Stokes  respiration).  Are  there 
any  changes  in  the  pupils?  Consult  several  text-books  to 
find  out  what  action  morphine  has  on  the  dog's  pupil. 
Would  the  administration  of  ether  to  a  dog  that  had  pre- 
viously received  a  dose  of  morphine  in  any  way  affect  the 
action  of  the  alkaloid  on  the  pupil  ?  Has  the  animal 's  tem- 
perature changed?  Keep  the  animal  in  a  quiet  place  (in 
a  metabolism  cage  if  possible)  until  next  day  and  follow 
the  course  of  the  drug's  action  as  fully  as  you  can.  Is 
the  recovery  complete?  How  long  does  this  require?  If 
the  animal  dies  what  will  be  the  immediate  cause  of  death? 
If  3^ou  succeed  in  collecting  any  urine  test  this  with  Bene- 
dict's modification  of  Fehling's  solution.  Do  you  get  a 
positive  test?  What  does  this  show?  If  you  do  not  have 
this  solution  use  Fehling's  or  Haines'  solution. 

EXPERIMENT  XXVI. 

Fehling's  Test  for  Reducing  Bodies. 

1.  Into  a  test  tube  pour  five  cubic  centimeters  each  of 
solutions  A  and  B.  Bring  the  mixture  to  a  boil.  Is  there 
any  change  from  a  clear  deep  blue  color?  If  so  the  solu- 
tion is  probably  decomposed.  If  no  change  of  color  and 
no  precipitate  forms  the    solution    is    satisfactory.     Add 


GENERAL  ACTIOI^   OF    MORPPIINE  177 

drop  by  drop  to  this  warm  solution  five  or  ten  drops  of 
the  nrine  to  be  tested.  Wait  a  little  while  and  if  no  reduc- 
tion (yellowish  or  reddish  precipitate)  appears,  then  again 
heat  the  mixture.  A  red  or  reddish-yellow  precipitate  in- 
dicates the  presence  of  reducing  bodies  in  the  urine.  (If 
no  precipitate  forms  at  once,  set  the  tube  aside  for  a  few 
minutes  and  observe  it  later.)  This  is  usually  due  to 
sugar,  but  other  substances  (e.  g.,  gh^curonic  acid,  etc.) 
may  .give  a  similar  reaction.  For  tests  to  differentiate  be- 
tween these  bodies  the  student  is  referred  to  text-books 
on  physiological  chemistry. 

EXPEEIMENT  XXVII. 

Morphine.     (Cat:  General  Symptoms,  Central  Nervous 

System.) 

1.  Inject  into  a  cat  subcutaneously  twenty-five  milli- 
grams of  morphine  sulphate  (or  the  hydrochlorate  or  ace- 
tate) per  kilogram  of  body  weight.  Observe  carefully  the 
symptoms  produced  by  the  drug  in  this  animal  and  com- 
pare them  with  those  exhibited  by  the  dog  that  was  in- 
jected with  morphine.  What  differences  do  you  note  as 
regards  the  pupils,  intelligence,  reflexes,  convulsive  tremors, 
etc.? 

EXPERIMENT  XXVIII. 

Morphine,  Codeine.    (Dog:  Respiration,  Blood-pressure, 
Oxygen  Consumption,  Urine.) 

1.  Arrange  a  dog  for  recording  blood-pressure  and  res- 
piration. Place  adrenaline  in  one  injecting  burette  (femo- 
ral vein)  and  a  morphine  salt  solution  (one  cubic  centi- 
meter equals  five  milligrams)  in  another  burette  (femoral 
vein).  The  dog  should  weigh  about  ten  or  twelve  kilos.  If 
you  do  not  have  suitable  apparatus  omit  the  oxygen  deter- 


178 


EXPERIMENTAL   PHARMACOLOGY 


Nasal 
Maxillary 

Lachrymal 


Temporal 


Interparietal 


Premaxlllary 
Malar 


Mastoid 


Suboccipital 


Fig.    169. — The    upper    surface    of    the    skull    of    a    cat.       (Partially    adapted    from    Jayne.) 


THE    CAT  S   SKULL 


179 


^  ;3^  -d 

J^       ™.      o" 


o> 

3 

M 

O 

^_ 

y» 

o> 

o 

1 

-1 

^ 

(n 

180 


EXPERIMENTAL   PHARMACOLOGY 


mination  and  proceed  with  the  remaining  observations. 
To  determine  marked  changes  in  the  rate  of  oxygen  con- 
sumption by  the  animal  an  apparatus  similar  to  that  shown 
in  Fig.  172  is  required.  (See  also  Fig.  175.)  This  con- 
sists essentially  of  the  anesthetic  apparatus  shown  in  Fig. 
116  but  with  the  addition  of  a  four  or  six  inch  thin  alumi- 
num (or  pasteboard)  disc  which  rests  (stuck  on  with  muci- 


Olfactory  lobe 


Crucial  fissure 


Lateral  sulcus 


Suprasylvian 
sulcus 


Great 

longitudinal 
fissure 


Gyrus  Margin  alls 
Gyrus  Suprasylvius 
Gyrus  Ectosylvius 


Vermis  of  cerebellum 

Medulla  oblongata 
ist  cervical  nerve 
Spinal  cord 
White  matter  of  cord 

Fig.    171. — Dorsal   surface   of  the   brain   of   a   cat.      (Partially  adapted   from   Davison.) 


Lateral  lobe  of 

cerebellum 


Posterior  pyramids 
Gray  matter  of  cord 


lage)  on  top  of  the  bath  cap  covering  the  large  pan  in  the 
bottom  of  which  is  placed  strong  (not  saturated)  sodium 
hydrate  solution  [Ca(0H)2  may  also  be  added  if  desired] 
to  the  depth  of  about  three-fourths  or  one  inch.  Oxygen  is 
run  into  the  breathing  pan  from;  the  tank  as  needed.  In 
the  center  of  the  aluminum  disc  are  two  small  holes  in 
which  is  tied  a  twine  string  about  four  feet  long.  One,  two 
or  three  bull-dog  forceps  must  usually  be  laid  on  the  top  of 
the  disc  to  cause  it  to  move  down  readily  as  the  dog  in- 
spires.   As  the  dog  expires  the  disc  moves  upward.    These 


RATE   OF   OXYGEN   CONSLTMPTION 


181 


^ooc.c. 
cylinder 


Fig.  172. — Arrangement  of  apparatus  for  recording  and  measuring  the  rate  of  oxy- 
gen consumption.  (See  also  Fig.  175.)  The  side  tube  of  the  tracheal  cannula  opens 
into  the  interior  of  the  large  square  pan.  The  trough  (Fig.  173)  is  filled  with  water 
and  the  breathing  pan  dips  up  and  down  in  the  water.  A  layer  (3/4  inch  deep)  of 
strong  sodium  or  potassium  hydrate  solution  is  placed  in  the  bottom  of  the  inner  pan 
to  absorb  the  CO2  exhaled  by  the  animal.  If  the  clip  on  the  tube  leading  from  the 
graduated  cylinder  to  the  pan  be  closed  while  the  oxygen  tank  is  opened  a  little,  the 
water  in  the  cylinder  will  be  forced  up  into  the  pressure  bottle.  When  the  cylinder  is 
thus  filled  with  oxygen  the  tank  valve  is  closed.  The  oxygen  remains  stationary  in  the 
cylinder  but  can  he  immediately  run  into  the  pan  by  opening  the  clip  on  the  com- 
municating rubber  tube,  as  the  water  in  the  pressure  bottle  will  quickly  run  down  and 
displace  the  oxygen  which  is  thus  forced  out  into  the  pan.  This  causes  the  writing 
lever  on  the  drum  to  make  a  sharp  rapid  descent.  As  the  animal  uses  up  the  oxygen 
and  the  breathing  pan  slowly  descends  the  writing  point  on  the  drum  slowlv  goes  up. 
(See  Fig.   175.)  -     5  1 


182 


EXPERIMENTAL   PHARMACOLOGY 


fairly  rapid  movements  up  and  down  correspond  to  the 
regular  respiratory  movements  of  the  animal.  But  in  ad- 
dition to  these  rapid  movements  a  larger  and  more  pro- 


Breafhinq   pan 


Inner  pan 
Trouqh  (water) 
Outer  pan 


Respiratory 
openinq 
NaOH  solution 
Hinqe  rod 
Oxyqen  inlet 
Ether  inlet 


T'  -irH3iis.chi. 


Fig.  173. — Inner  construction  of  the  pans  shown  in  Fig.  172.  These  pans  can  be 
made  of  sheet  brass  or  tinned  iron.  Pans  which  can  be  used  for  the  purpose  can  ofteri 
be  purchased  at  a  hardware  store  (or  a  ten  cent  store).  (See  Journal  of  Laboratory  and 
Clinical  Medicine,   1916,  ii,  p.   145;  also  ibid,   1916,  ii,  p.   94.) 


Stopper 


_S  Inches 


13  xlZ 


Fig.  174. — Lateral  view  of  a  cross-section  of  the  apparatus  shown  in  Fig.  172.  The 
breathing  pan  is  best  made  of  very  thin  sheet  brass  (which  is  easily  soldered  and  is  not 
affected  by  alkalies  as  is  aluminum).  The  pan  should  be  carefully  counterpoised  with 
an  adjustable  weight.      The   dimensions  are  indicated  in  inches   on   the   scale. 

longed  movement  of  the  disc  occurs.  This  corresponds  to 
the  injection  of  oxygen  from  the  tank  into  the  pan  when 
the  disc  will  be  lifted  up  a  considerable  distance  (perhaps 


EATE   OF   OXYGEN   CONSUMPTION 


183 


one  inch),  and  then  to  the  gradual  consumption  of  this 
oxygen  by  the  dog  during  which  interval  the  disc  will  be 
falling  (one  inch).  During  all  this  time  the  exhaled  car- 
bon dioxide  is  being  absorbed  by  the  alkali  solution.  The 
twine  string  attached  to  the  disc  passes  over  two  pulleys 
(one  inch  brass  wheels — these  should  be  of  the  best  quality 
and  can  be  bought  at  any  good  hardware  store  for  about 
twenty  or  thirty  cents  apiece).     The  opposite  end  of  the 


Fig.  175. — A  simpler  arrangement  for  recording  the  rate  and  amount  of  oxygen 
consumption  by  an  animal.  (See  also  Fig.  172.)  There  is  more  chance  for  "lost  mo- 
tion" by  use  of  the  flexible  bath  cap  over  the  pan  than  with  the  apparatus  shown  in 
Fig.    172.      (See  Journal   of  L,aboratory   and   Clinical   Medicine,    1916,    ii,    p.    94.) 


string  is  clamped  on  to  the  long  arm  of  a  frog  heart  lever 
by  means  of  a  bull-dog  clamp.  Two  clamps  may  be  needed 
to  draw  the  lever  doA\m  readily.  These  clamps  serve  not 
only  to  hold  the  string  to  the  lever  but  act  as  balancing 
weights  as  well.  The  heart  lever  writes  at  the  top  of 
the  drum,  below  this  is  the  blood-pressure  (mercury  ma- 
nometer), next  the  respiration  (tambour  connected  to  the 


184  EXPERIMENTAL   PHARMACOLOGY 

stetliograph  drum),  and  at  the  bottom  is  the  base  line  and 
time  marker.  The  drum  should  have  an  approximately 
constant  slow  speed. 

The  arrangement  of  the  apparatus  and  records  is  shown 
in  Fig.  175.  The  anesthesia  should  be  fairly  light  and 
maintained  solely  with  ether  (since  morphine  is  injected 
later).  If  the  apparatus  is  in  good  condition  the  anesthe- 
sia will  be  approximately  constant.  Observe  the  character 
of  the  tracing  on  the  drum,  also  Fig.  180.  The  thin  narrow 
curved  lines  in  the  oxygen  consumption  record  are  made 
while  the  drum  is  standing  still.  This  narrow  line  repre- 
sents the  downward  movement  of  the  lever  as  the  pan  is 
filled  with  oxygen.  The  extent  of  this  down  stroke  is  op- 
tional but  should  be  regulated  by  the  tension  of  the  oxygen 
on  the  bath  cap.  The  cap  should  not  be  filled  so  full  as 
to  stretch  it,  as  this  would  cause  too  great  a  mechanical 
obstruction  to  the  breathing  of  the  animal.  This  must  be 
carefully  avoided.  When  the  pan  is  filled  sufficiently  with 
oxygen  the  writing  lever  will  have  descended  to  a  certain 
level  on  the  drum.  This  level  marks  what  may  be  termed 
the  lower  base  line  for  the  ox3^gen  record.  In  filling  the 
pan  mth  oxygen  at  all  later  times  see  to  it  that  the  lever 
again  descends  to  this  same  level  as  nearly  as  you  can  de- 
termine. This  is  done  by  watching  the  lever  go  down  as 
oxygen  is  run  in  very  cautiously.  Conversely  the  highest 
point  in  the  oxygen  record  may  be  called  the  upper  base 
line  for  this  record.  If  while  the  drum  is  stopped  the  lever 
be  run  doA\m  to  the  lower  base  line  by  adding  oxygen  to  the 
pan,  then  just  as  the  lever  reaches  the  base  line  the  injec- 
tion of  oxygen  is  stopped  and  the  drum  is  started.  (It  is 
desirable  that  the  drum  start  quickly  and  soon  reach  the 
maximum  for  that  rate  of  speed.)  As  the  drum  runs  the 
lever  moves  up  and  down  a  short  distance  rapidly  at  each 
inspiration  and  expiration.  We  are  not  much  concerned 
now  with  these  short,  rapid  movements  as  they  correspond 
fairly  closely  with  the  respiration  tracing  from  the  stetho- 


THE   GENERATION   OF   OXYGEN 


185 


Mercury  bulb 
^      ^:\r^^^        or  funnel 


To  anesfhefic 

device  or  to 

reservoir 


UmiA 


Fig.  176. — A  cheap  form  of  apparatus  used  for  making  pure  oxygen.  Sodium  per- 
oxide is  placed  in  the  left  hand  bottle  and  water  is  allowed  to  drop  slowly  down  on  to 
the  NaoQo  from  the  mercury  bulb  above.  Oxygen  is  liberated  and  at  once  bubbles  over 
through  the  water  in  the  wash  bottle.  In  one  experiment  74  grams  of  sodium  peroxide 
generated  sufficient  oxygen  to  run  a  IS  kilo  dog  for  one  hour.  At  the  end  of  this  period 
the  left  hand  bottle  was  exchanged  for  a  second  (quart  milk  bottle)  containing  a  sec- 
ond 74  grams  of  sodium  peroxide  and  this  again  liberated  sufficient  oxygen  to  run  the 
animal  another  hour.  In  this  experiment  the  closed  anesthesia  apparatus  shown  in  Fig. 
116  (see  also  Fig.  17S)  was  used.  It  is  advisable  to  use  some  kind  of  reservoir  to  catch 
the  oxygen  generated  as  the  rate  of  liberation  cannot  be  controlled  accurately  by  the 
addition  of  the  water. 


186 


EXPERIMENTAL   PHARMACOLOGY 


graph  drum.  These  movements  do,  however,  with  many 
drugs,  record  very  profound  and  striking  changes  in  the 
bronchioles.  (Can  you  detect  any  evidence  of  this  when 
morphine  is  injected  into  the  femoral  vein!)  But  the  im- 
portant point  in  the  oxygen  record  is  the  gradual  rise  of 
the  lever  as  the  oxygen  in  the  pan  is  consumed  by  the  dog. 
The  rate  of  this  rise  determines  the  rate  of  oxygen  con- 
sumption. Watch  carefully  and  when  the  lever  reaches  a 
satisfactory  altitude  (this  will  vary  with  each  experiment 
and  the  student  with  a  little  practice  can  estimate  about 
when  to  stop),  which  will  generally  be  about  two  inches 
if  a  large  drum  is  used  (lower  and  less  magnified  if  a 
small  drum  is  used),  then  suddenly  stop  the  drum  and  at 


Rubber  bath  cap 


Cas  iniet 


\9i//7.  Cal^e  psn 
Flan(jeon  pan 
Added  flanqe 


03S  out  lev 


Fig.  177. — A  simple  gas  reservoir  made  from  a  very  shallow,  wide,  round  cake  pan 
with  two  spouts  soldered  into  the  walls.  A  large  bath  cap  is  stretched  over  the  pan 
and  serves  to  form  an  adjustable  gas  reservoir  suitable  for  use  with  the  apparatus 
shown  in  Fig.  176.  A  small  spirometer  (1  or  2  gallons)  may  also  be  used  as  a  reservoir. 
The  spirometer  should  be  delicately  counterpoised  as  the  oxygen  is  not  delivered  from 
the  wash  bottle  under  a  high  pressure.  A  large,  thin  walled  rubber  bag  may  also  be 
used. 


once  run  a  fresh  sujDply  of  oxygen  into  the  pan.  The  lever 
comes  down  and  when  the  base  line  is  reached  stop  the 
oxygen  inflow  and  immediately  start  the  drum.  (If  the 
drum  is  exceedingly  slow  the  oxygen  can  be  run  in  while 
the  drum  is  turning.  This  is  very  convenient.)  When  the 
lever  again  reaches  its  former  high  point  stop  the  drum 
and  at  once  reinject  ox^^gen.  This  gives  a  saw-tooth  like 
record.  And  the  distance  between  each  two  consecutive 
teeth  or  descending  narrow  lines  in  the  record  gives  a 
measure  of  the  relative  amount  of  oxygen  consumed  dur- 
ing that  period  of  time.     If  a  drug  which  slows  the  con- 


OXYGElSr   DETERMINATION 


187 


sumption  of  oxygen  is  given,  then  the  distance  between 
the  consecutive  descending  lines  will  be  increased;  while 
a  drug  which  increases  the  relative  consumption  of  oxy- 


suction  apparatus 


-Large  glass  tube  or  Liebig  condenser 
with  graduated  scale  (c.c.) 


By  pass 


Fig.  178. — Dreser's  arrangement  of  apparatus  for  recording  the  volume  of  air  ex- 
pired by  an  animal  in  a  given  length  of  time.  The  large  glass  tube  (or  Liebig  con- 
denser jacket;  is  filled  with  water  which  is  supported  up  in  the  tube  by  the  pressure 
of  the  atmosphere.  The  by-pass  is  closed  and  the  clip  on  the  tube  leading  from  the 
milk  bottle  inspiratory  valve  is  removed.  When  the  animal  inspires,  air  enters  the  in- 
spiratory tube,  bubbles  through  the  water  in  the  bottom  of  the  bottle  and  thence  passes 
to  the  lungs.  At  expiration  the  air  passes  through  the  straight  course  of  the  tubes  to 
the  large  glass  jar  or  dish  and  thence  is  liberated  in  the  lower  end  of  the  large  glass 
tube.  The  exhaled  air  then  quickly  displaces  the  water  and  rises  to  the  upper  part  of 
the  large  glass  tube  where  it  can  be  measured  on  the   scale. 


1^ 


EXPERIMENTAL   PHARMACOLOGY 


gen  will  cause  a  decrease  in  the  distance  between  consecu- 
tive descending  lines. 

If  the  instructor  desires  it  is  an  easy  matter  to  place  a 
gas  measuring  device  in  the  path  of  the  oxygen  inflow  tube 


To  recording 
fdmbour 


Mercury  bulb 


^Bladder  cannula 

^niiiiiijjwwwm)  ->  info  beaker 
or  to  recorder 


Urachus 
Loose  liqafure 


Fig.    179. — Technic    for    inserting   a    bladder   cannula    or    for    connecting    a    mercury    bulb 
to  record  bladder  contractions.      (For  discussion  see  text.) 

and  measure  the  amount  of  oxygen  run  in  at  each  filling 
of  the  pan  (see  Fig.  172).  This  is  instructive  and  is  a 
valuable  procedure  in  the  beginning,  but  with  a  little  prac- 
tice the  operator  will  be  able  to  attain  sufficient  accuracy 


RATE   or    OXYGEN   CONSUMPTION  189 

by  simply  watching  the  lever  as  it  writes  on  the  drum.  A 
monkey  wrench  is  better  than  the  regular  wheel  wrench  to 
control  the  valve  on  the  oxygen  tank  where  careful  regu- 
lation is  needed.  It  is  very  desirable  to  have  the  tank 
fastened  down  with  a  clamp  to  the  table  (see  Figs.  112  and 
113). 

To  obtain  urine  for  tests  the  abdomen  is  opened  over  the 
bladder  which  is  caught  in  a  hemostat  at  the  urachus  (Fig. 
179).  The  bladder  is  then  raised  a  little  and  a  second 
hemostat  is  clamped  on  the  opposite  side  of  the  urachus 
in  such  a  manner  that  an  opening  can  be  cut  with  a  scalpel 
or  scissors  just  between  the  tips  of  the  hemostats.  Be- 
fore this  opening  is  made  place  a  twine  string  around  the 
upper  part  of  the  bladder  (just  below  the  points  of  the 
hemostats)  and  tie  it  loosely.  Open  the  bladder  (do  not 
allow  any  urine  to  escape  or  blood  to  run  doA\ai  into  the 
bladder  if  it  can  be  avoided)  and  quickly  insert  the  blad- 
der cannula.  Tie  the  ligature  and  replace  the  bladder 
within  the  abdomen  which  is  closed  by  hemostats.  Catch 
the  urine  in  a  beaker  and  test  some  early  to  see  if  it  con- 
tains glucose. 

^¥lien  all  apparatus  is  adjusted  start  the  drum  and 
take  several  records  of  the  ox^^gen  consumption  in  order 
to  become  familiar  with  the  method  and  to  get  some  nor- 
mal records.  Your  success  mil  depend  largely  on  your 
ability  to  determine  exactly  when  to  stop  and  start  the 
drum  and  to  judge  when  the  lever  has  gone  high  enough. 
This  is  the  most  diffcult  part  of  the  experiment  and  should 
alivays  be  done  by  that  member  of  the  group  who  is  best 
able  to  carry  out  this  work. 

Your  "normal"  oxygen  records  should  be  almost  exactly 
alike  both  in  form  and  in  the  distance  the^^  occup}^  on  the 
drum. 

Inject  one  cubic  centimeter  of  morphine.  Watch  the 
oxygen  records  closely  and  make  your  changes  promptly. 
When  the  records  all  return  to  normal  inject  three  or  four 


190  EXPERIMENTAL   PHAEMACOLOGY 

cubic  centimeters  and  record  the  results.  Do  you  get  what 
you  expected?  Does  the  anesthesia  remain  regular?  How 
are  the  respiratory  movements  affected?  Does  the  rate 
of  oxygen  consumption  correspond  with  the  rapidity  or 
slowness  of  the  respiratory  movements  or  with  the  height 
of  the  blood-pressure?  Would  you  have  expected  these  re- 
sults ?  Now  take  one  or  two  normal  oxygen  records  and 
then  when  the  oxygen  lever  is  getting  pretty  well  up  to 
the  top  of  its  course  inject  one-half  cubic  centimeter  of  ad- 
renaline. Watch  carefully  to  reset  your  oxygen  record  at 
the  exact  moment.  Be  sure  before  the  adrenaline  is  in- 
jected that  the  rise  in  the  manometer  writing  point  ivill 
not  interfere  (catch)  luith  your  oxygen  lever.  Watch  your 
oxygen  record  closely  and  make  the  changes  promptly. 
Take  at  least  two  or  three  minutes  to  record  this  after  the 
adrenaline  is  injected.  Do  you  observe  any  peculiar 
changes  in  your  records?  If  not,  wait  a  while  and  repeat 
the  adrenaline  injection. 

How  does  morphine  affect  the  heart?  Can  you  detect 
any  change  in  the  rate  ?  Give  more  morphine  from  time 
to  time  (two  cubic  centimeters  per  dose),  and  see  if  you 
can  bring  on  a  Cheyne-Stokes  form  of  respiration.  Does 
the  anesthesia  become  any  deeper?  Examine  the  pupils 
carefully.  Are  they  in  the  same  condition  as  were  those 
of  the  dog  in  Experiment  XXV?  Does  this  agree  Avith  the 
text-book  descriptions? 

Inject  as  much  morphine  as  you  think  (from  the  ap- 
pearance of  the  respiration,  blood-pressure,  etc.)  the  ani- 
mal can  safely  stand.  You  may  not  get  a  Cheyne-Stokes 
form  of  respiration,  but  many  small  repeated  doses  are 
very  liable  to  bring  it  on.  Variable  but  constantly  repeated 
irregularities  of  the  respiration  often  appear. 

Allow  the  animal  to  recover  a  little  if  it  will  and  then 
inject  codeine  (two  cubic  centimeters — 1  c.c.  =^  5  mg.).  Get 
a  record  of  this  and  then  increase  the  dose  given.  After 
a  few  injections  (and  within  half  an  hour),  marked  symp- 


M' 


ACTION  OF  MOEPKINE  ON  OXYGEN  CONSUMPTION  191 


192 


EXPERIMENTAL    PHARMACOLOGY 


toms  should  appear.  Test  the  urine  for  glucose.  Is  there 
any  reduction?  How  do  you  account  for  this!  Kill  the 
animal  with  codeine. 

2.  If  time  permits  carry  out  the  following  dissections. 


Fig.  181. — Record  showing  the  action  of  adrenaline  on.  the  rate  of  oxygen  consump- 
tion, uterine  contractions,  blood-pressure  and  respiration.  There  is  a  slight  slowing 
down  of  the  rate  of  consumption  of  oxygen  which  is  mainly  concordant  with  the  Period 
occupied  by  the  fall  in  blood-pressure  after  tl:e  large  initial  rise.  (See  Journal  ot  i^ab- 
oratory   and    Clinical    Medicine,    1916,    ii,    145.) 

Isolate  both  the  internal  and  the  external  jugular  veins 
on  each  side.  (See  Figs.  133  and  183.)  Note  carefully  in 
just  what  portion  of  the  neck  tissues  these  vessels  are 


PRACTICE    DISSECTION  1^6 

located.  Could  you  pass  a  large  needle  in  at  the  median 
incision  in  the  neck  and  then  push  it  out  through  the  tis- 
sues in  the  side  of  the  neck  in  such  a  manner  as  to  in- 
clude both  the  jugulars  on  one  side  in  a  ligature  threaded 
through  the  eye  of  the  needle!  If  you  should  thus  tie  a 
ligature  loosely  around  a  portion  of  the  tissues  in  the 
side  of  the  neck  (including  both  veins),  and  then  should 
lift  up  with  a  moderate  degree  of  pressure  on  the  ligature, 
what  eifect  Avould  this  have  on  the  back  flow  of  blood 
through  the  veins  to  the  heart?  How  much  pressure  does 
it  take  to  shut  off  the  flow  through  a  vein?     Carry  your 


Cervical  nerves 


Diaphragm 


Vaqo- 
symp. 
frunK-^ 


Cervical 
vertebrae 


Fig.    182. — Schematic    representation    of    the    origin,    course    and    distribution    of   tiie    right 
phrenic  nerve  in  a  dog.     (Tlie  origin  varies  in  different  animals.) 


dissection  well  down  on  to  the  longus  colli  muscle  in  the 
right  side  of  the  neck  (Fig.  184)  and  find  the  right  verte- 
bral artery.  Pass  a  large  aneurism  needle  under  the  ves- 
sel, lift  it  up  and  slip  a  ligature  around  it.  What  is  the 
distribution  of  this  vessel?  Could  you  inject  a  solution 
from  a  hypodermic  syringe  into  this  vessel  toward  the 
head?  How  long  a  space  would  you  have  to  operate  on 
the  vessel?  If  you  do  not  find  it  readily,  pick  up  the  right 
subclavian  artery  and  find  the  vertebral  from  this.  Could 
you  make  the  dissection  tvitliout  getting  into  the  chest  cav- 


194  experimeinttal  pharmacology 

ityf  Pick  up  the  right  phrenic  nerve.  What  is  the  origin 
of  this  nerve?  If  you  do  not  find  it  readily  open  the  chest 
and  locate  it  on  the  pericardium  at  the  side  of  the  heart. 
Trace  it  from  here  back  up  into  the  neck.  Could  you  cut 
both  phrenics  in  the  neck  ivithoiit  opening  the  chestf  This 
is  sometimes  done  to  stop  movements  of  the  diaphragm 
when  these  interfere  with  certain  records  that  are  being 
made. 

EXPERIMENT  XXIX. 

Morphine,  Codeine,  Pantopon,  Heroine,  Peronine,  Dionine, 
Narcotine  or  Thebaine.    (Spinal  Dog:   Bronchioles.) 

1.  This  is  a  neAv  field  of  experimentation  for  most  med- 
ical schools.  Many  drugs  act  vigorously  on  the  bronchioles 
and  it  is  unfortunate  for  medical  students  not  to  have 
some  opportunity  to  perform  experiments  to  bring  out 
these  results,  for  the  action  of  these  drugs  is  often  much 
more  striking  on  the  bronchioles  (and  perhaps  frequently 
as  important)  than  are  the  corresponding  actions  on  the 
heart  or  other  organs.  Several  methods  will  therefore  be 
given  in  different  experiments  in  order  to  give  every  lab- 
oratory a  chance  to  carry  out  such  experiments.  The  best 
(but  perhaps  the  most  complicated)  method  will  be  given 
in  Experiment  LXX.  For  peripherally  acting  drugs  it  is 
advisable  to  use  spinal  dogs.  (Cats  may  also  be  used  for 
this  work  but  dogs  are  better.) 

Before  starting  the  experiment  be  sure  to  arrange  for 
a  reliable  source  of  artificial  respiration.  This  should  be 
from  an  artificial  respiration  machine,  but  a  hand-bellows 
fixed  to  open  only  a  given  distance  (to  regulate  the  stroke) 
may  answer. 

Etherize  a  dog  and  arrange  it  for  a  blood-pressure  trac- 
ing. Place  injecting  burettes  in  connection  with  the  fem- 
oral veins.  One  burette  contains  adrenaline  (1:10,000), 
the  other  an  opium  alkaloid.    Any  one  of  those  at  the  head 


Exijuqulzr  vein 
Carotid  artery  - 
Int.  ju^u/ar  v. 


Transverse  scdpular  sna 

cervical  ascenc/m^  arteries 

Subclavian  vein 


Fig.    183. — Dissection    of   the    lower   part    of   the   neck    and    upper   part    of    the   chest   on    the 
right   side   in   a   dog.      (Modified   from    Schniiedeberg.) 


Ext.  juqukr  vein  -^ 
Carotid  artery  — v^ 
Int  jugular  vein-^^^ 
Va(]o  sympathetic 

nerve  — ^ 
Vertebral  artery^ vein ^  "^ 

Deep  cervical  artery  —^ 


Transverse  scapular  ^  ,       , 

ascending  cervical  drteries-       \ 

Rt  subclavian   artery^ 


Rt  mammary  artery 


Fig.    184. — Dissection    of    the    lower    part    of    the   neck    and   upper    part    of   the    chest    and 
of    the    axillary    region    in    a    dog.       (Modified    from    Schmiedeberg. ) 


BRONCHIAL  ACTION   OF   OPIUM   ALKALOIDS  195 

of  this  section  may  be  used,  but  either  heroine,  codeine  or 
dionine  will  probably  give  the  best  results.  Be  sure  the 
drug  is  fresh  and  of  first-class  quality.  Codeine  possesses 
some  advantages  in  this  respect.  The  strength  of  the  solu- 
tion chosen  should  be  five  milligrams  to  the  cubic  centi- 
meter. 

With  great  care  to  avoid  opening  the  chest  at  the  apex 
dissect  down  on  the  right  side  of  the  neck  (see  Experiment 
XXVIII,  2;  also  Figs.  183  and  184),  and  pick  up  the  right 
vertebral  artery.  Place  a  ligature  around  the  vessel  and 
tie  the  ligature  once  loosely.  The  ends  of  this  ligature  are 
brought  together  and  clamped  Avith  a  bidl-dog  so  it  can 
be  found  readil}^     Noav  with  a  large   (five  or  six  inch) 


Fig.    185. — Large   needles    for   sewing   with    heavy    twine. 

needle  (Fig.  185)  pass  a  ligature  of  heavy  twine  through 
the  tissues  in  the  side  of  the  neck  in  such  a  manner  that 
both  jugular  veins  will  be  included.  The  carotid  artery 
and  vagus  nerve  must  not  be  included.  The  ligature  passes 
out  through  the  skin  at  the  side  of  the  neck.  The  two  ends 
of  the  ligature  are  brought  together  and  tied  once  loosely 
and  clamped  with  a  hemostat.  Another  ligature  is  simi- 
larly placed  on  the  opposite  side  so  that  in  this  way  the 
chief  venous  return  flow  from  the  head  can  be  quickly 
clamped  off.  Now  fill  a  small  syringe  (two  cubic  centi- 
meters) of  good  quality  with  chloroform.  The  point  of  the 
syringe  should  be  as  small  and  as  short  as  possible.  A 
cheap  syringe  is  very  liable  to  leak  chloroform.  Get  all 
apparatus  properly  adjusted  and  then  lift  up  the  vertebral 
arter}^  on  an  aneurism  needle  and  insert  the  syringe  point 


196 


EXPERIMENTAL   PHARMACOLOGY 


into  the  lumen  of  the  artery  pointing  toward  the  animal's 
head.  This  should  be  done  with  great  care  and  no  chloro- 
form should  he  emptied  out  in  the  ivall  of  the  vessel.  The 
assistant  now  takes  hold  of  the  ligatures  (hemostats)  that 


Fig.  186. — Brass  tube  (7yi  inches  long  and  ^i  inch  in  diameter)  with  (separable) 
spear  point  to  be  passed  through  the  chest  for  recording  lung  volume  changes.  The 
holes  cover  a  space  about  2>4    inches  long. 

control  the  jugular  veins  and  gets  ready  to  close  off  (by 
pressure)  these  vessels.  It  is  advisable  for  a  second  as- 
sistant to  put  a  hull-dog  clamp  on  the  left  carotid  at  this 
moment.     The  operator  then  injects  the  chloroform  (one 


Fig.    187.- — Arrangement    of    animal    for    recording    lung    volume    changes.       (For    descrip- 
tion  see   text.) 


or  two  cubic  centimeters)  into  the  vertebral  artery.  This 
chloroform  quickly  reaches  the  brain  and  destroys  all  parts 
with  which  it  comes  in  contact.     The  blood-pressure  falls 


CHLOROFORM   INJECTIOIST   INTO   VERTEBRAL  ARTERY 


197 


rapidly  and  artificial  respiration  must  be  started  at  once. 
Close  off  the  jugulars  immediately  and  tie  the  ligatures 
firmly.  Be  sure  the  lungs  are  well  inflated  but  do  not  burst 
them.  Remove  the  ether  quickly  as  no  further  anesthetic 
is  needed.  If  your  first  injection  does  not  succeed  well, 
make  a  second  one  into  the  left  carotid  artery.    Luckhardt 


Cenhqrade 
fhermomei-er 


7?  TtHalleek- 


Fig.  188. — Arrangement  of  apparatus  for  keeping  the  systematic  blood-pressure  at  a 
constant  level  during  the  action  of  drugs  which  produce  marked  changes  in  the  caliber 
of  the  arterioles.  The  cannulas  in  the  femoral  arteries  are  connected  with  a  siphon  tube 
which  dips  in  a  beaker  containing  warmed  salt  solution  (or  whipped  or  hirvidinized 
blood).  Hirudin  is  injected  intravenously  to  prevent  clotting  of  the  blood.  The  alti- 
tude of  the  beaker  above  the  animal  regulates  the  pressure  which  can  be  maintained 
in  the  blood  vessels.  This  is  read  off  from  the  mercury  manometer.  If  the  vessels 
contract  blood  is  forced  over  into  the  beaker  but  the  arterial  pressure  does  not  rise. 
When  the  vessels    (arterioles)    dilate   the   blood   siphons   back  into   the  femoral   arteries. 

has  succeeded  well  by  making  injections  into  the  carotid 
artery  alone.  (Some  workers  have  obtained  good  results 
by  injecting  a  three  per  cent  suspension  of  starch  gran- 
ules into  the  carotid  artery.)  This  is  easier  than  inject- 
ing the  vertebral  on  account  of  the  dissection,  but  the  me- 
dulla may  not  be  well  reached  thronoli  the  carotid.     In  a 


198 


EXPEKIMENTAL   PHARMACOLOGY 


Fig.  189. — This  lung  volume  and  blood-pressure  record  was  taken  from  a  dog  by  the 
use  of  the  blood-pressure  regulating  device  shown  in  Fig.  188.  The  lung  record  was 
taken  by  means  of  (positive)  artificial  respiration  (using  the  tube  shown  in  Fig.  186  and 
the  method  illustrated  in  Fig.  187).  The  purpose  of  the,  tracing  was  to  show  that  con-- 
traction  or  dilatation  of  the  bronchioles  is  practically  entirely  independent  of  the  changes 
in  systemic  blood-pressure.  The  slight  variations  in  the  course  of  the  carotid  pressure 
tracing  were  due  to  the  great  suddenness  of  the  extensive  changes  in  caliber  of  the 
arterioles  produced  by  the  action  of  the  drugs,  i.  e.,  the  contraction  of  the  arterioles 
occurred  slightly  quicker  than  the  blood  could  siphon  over  through  the  small  pointed 
cannulas  into  the  beaker.  But  if  no  equalizing  device  had  been  used  the  carotid  pressure 
would  have  risen  above  the  top  of  the  lung  tracing. 


BRONCHIAL  ACTION   OF   OPIUM   ALKALOIDS 


199 


spinal  dog  the  blood-pressure  will  be  about  one  inch  above 
the  base  line  on  the  drum.  Do  not  be  alarmed  so  long  as 
it  remains  this  high  and  is  not  falling.  If  any  of  the  chloro- 
form gets  back  to  the  heart,  the  dog  may  die  quickly.  If 
the  animal  is  about  to  die  inject  one-half  or  one  cubic 


^m     ^|_^""»*«- 


daiQij   ti^y^u       ^nyjurr-xl/L 


Fig.  190. — Blood-pressure  and  bronchiole  tracings  showing  the  action  of  morphine 
in  a  dog.  These  tracings  were  made  by  the  method  described  in  Experiment  LXX,  page 
287. 


centimeter  of  adrenaline.  AVhen  the  blood-pressure  is  reg- 
ular, then  pass  a  brass  tube  (Fig.  186)  directly  through 
the  chest  walls  at  the  level  of  the  ventral  border  of  the 
sixth  intercostal  space  (see  Fig.  187).     To  do  this  make 


200 


EXPEKIMENTAL   PHAKMACOLOGY 


an  incision  through  the  skin  on  each  side  in  the  proper 
place.  Then  pnsh  the  spear  point  of  the  tube  right  through 
the  muscular  walls  from  side  to  side.  Do  this  as  the  lungs 
are  deflated.  Be  sure  the  tube  passes  inside  the  chest  cav- 
ity and  does  not  slip  along  under  the  parietal  pleura  just 


mm 


I  |'i|1ii       s^Mi 


f    I 


IfufiMlM    illiUJ 


(ii  (Si  i  I  1  ,  r\  nnn 


J- 1  0,000 


mmmm 


j,^^i 


-^t^ft-e.-  S ^.exi^crv^^jiJ. 


Fig.  191. — Blood-pressure  and  bronchiole  tracings  showing  the  action  of  pantopon. 
(Pantopon,  or  pantopium  hydrochloricum,  is  the  hydrochloric  acid  extract  of  the  total 
alkaloids  of  opium — very  soluble  in  water,  sold  by  I-Ioffmann-L,aRoche  Chemical  Works, 
New  York.) 


BKONCHIAL  ACTIOjST   OF   OPIUM  ALKALOIDS 


201 


below  the  sternum.  Eemove  the  spear  point  from  the  tube 
and  place  on  this  end  a  piece  of  rubber  tubing  carrying  a 
screw  clamp.  This  is  to  regulate  the  amount  of  air  going 
into  the  tambour  which  is  attached  to  the  other  end  of 
the  tube.    Clamp  the  brass  tube  tightly  in  the  chest  walls 


iniiniiiiiiiiiininiii 


.2al — >>i 


3c^ 


^&^^^^/^^-9.U-(^^, 


iUHRS^BI^ 


„^   .^1^-  „1 92.— -Blood-pressure    and    bronchiole    tracings    showing    the    action    of    peronine. 
iipinme      tailed  to  cause   dilatation   of  the  bronchioles   and   the   animal   died   of   asphyxia. 
1.  could  easily   have  been   saved  by   forcibly   dilating  the   lungs   mechanically   to   check  the 
asphyxia. 


202 


EXPEKIMENTAL   PHARMACOLOGY 


by  hemostats  on  each  side.  The  tambour  should  have  a 
large  bowl  (three  inches,  see  Fig.  14).  Bring  the  writing 
point  of  the  tambour  on  to  the  drum  above  the  blood-pres- 
sure and  adjust  the  tambour  to  give  a  tracing  about  two 
or  three  inches  high.  The  force  of  the  respiration  may 
have  to  be  changed  to  give  this.     The  rate  of  inflations 


"'^'^■Yrwi'mm 


Fig.  193. — Blood-pressure  and  bronchiole  tracings  showing  the  action  of  dionine. 
Adrenaline  caused  a  prompt  dilatation.  The  method  used  is  described  in  Experiment 
LXX,  p.  287. 


should  be  about  twenty  or  twenty-five  times  per  minute. 
Start  off  the  drum  (slow  speed)  and  take  one  or  two  inches 
of  normal  record.  Then  inject  five  cubic  centimeters  of 
the  opium  alkaloid  solution.  The  blood-pressure  falls  at 
once  but  the  heart  should  not  stop.    What  does  the  lung 


BRONCHIAL  ACTION   OF   OPIUM   ALKALOIDS 


203 


volume  show?  Did  you  get  what  you  should  get?  AVhen 
the  action  of  the  drug  has  become  very  marked  inject  one 
cubic  centimeter  of  adrenaline.  How  does  this  affect  the 
blood-pressure  and  lung  volume?     Does  the  one  depend 


J-tO,OGO 


^^^^^^^^^^^^i 


Fig.    194. — Blood-pressure    and    bronchiole    tracings    showing    the    action    of   narcotine. 

on  the  other?     (They  do  not — each  is  mainly  independent 
of  the  other;  see  Figs.  188  and  189). 

When  the  records  again  become  normal  then  inject  six 
cubic  centimeters  more  of  the  opium  alkaloid.  Do  you  get 
a  second  lung  volume  tracing?    Inject  some  adrenaline  to 


204 


EXPERIMEE^TAL   PHARMACOLOGY 


revive  the  animal.  Now  stimulate  each  vagus  nerve  in 
the  neck  to  see  the  effect  on  the  heart  and  lungs.  What 
is  the  innervation  of  the  heart  and  bronchioles!  If  the 
animal  is  still  in  a  suitable  condition,  inject  six  cubic  centi- 
meters of  a  different  opium  alkaloid.  Do  you  get  lung 
records'?  Give  some  adrenaline  to  help  revive  the  animal. 
The  abdomen  may  now  be  opened  by  a  three  inch  median 


fArs4i»\JU.<^\    \  rec 


iiimirftiiMiiiiiimnriiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii 


Fig.  195. — Respiratory  and  blood-pressure  tracings  from  a  dog  showing  the  progres- 
sive actions  of  narcophine  (Straub),  narcotine  and  morphine.  The  peculiar  irregularity 
of  the  respiration  is  developed  early  and  leads  to  the  Cheyne-Stokes  type  of  respiration. 
What  is  the  cause  of  Cheyne-Stokes  respiration?  Does  the  peripheral  action  of  these 
drugs  (note  the  size  of  the  doses)  have  anything  to  do  with  the  respiratory  disturbances? 
The  vagi  were  intact. 


longitudinal  incision  down  near  the  pubic  symphasis  and 
the  bladder  lifted  up  as  described  in  Experiment  XXVIII, 
page  189.  The  animal  will  probably  be  dead  by  this  time. 
Could  you  thus  pick  up  the  bladder  and  place  a  cannula 
in  it  in  this  manner  in  a  spinal  dog  without  letting  the  ani- 


ACTION    OF    CAiSTNABIS    INDICA 


205 


mal  die?  How  iniglit  you  do  such  an  experiment  and  avoid 
opening  the  abdomen  after  the  brain  of  the  animal  was 
destroyed!  What  are  the  main  differences  that  you  note 
between  the  reactions  and  vitality  of  a  spinal  dog  as  com- 
pared with  a  normal  animal  I 


Fig.  196. — Method  of  administering  capsules,  pills  or  tablets  to  dogs.  The  tongue 
is  pulled  forward  and  the  prepared  dose  is  dropped  far  back  in  the  mouth.  The  jaws  are 
held  closed  and  the  animal  is  gently  slapped  under  the  throat,  or  a  little  water  may  be 
given.  The  method  illustrated  is  frequently  used  in  testing  (standardizing)  cannabis 
indica  preparations.  The  U.S. P.  doses  are: — fluidextract  0.03  cubic  centimeter,  extract 
0.004  gram  and  tincture  0.3  cubic  centimeter  per  kilogram  of  body  weight,  for  small  or 
medium-sized,  smooth-haired  (preferably  fox  terrier)  dogs.  Doses  not  larger  than  these 
should  produce  incoordination  (best  observed  when  the  animal  is  standing  still)  and 
slight  ataxy  in  walking.  The  animal  should  be  kept  in  a  quiet  room  and  the  symp- 
toms may  not  become  marked  (or  even  perceptible)  for  one  or  two  hours.  In  three  or 
foiir  hours  the  symptoms  entirely  disappear.  The  administration  of  3/4  grain  of  "can- 
nabinole"  in  oil  (in  globules)  to  a  dog  weighing  about  4  to  6  kilos,  is  recommended  for 
demonstrating  marked  symptoms.  (For  the  method  of  standardization  of  cannabis 
indica,  see  U.S. P.,  ix,  page  605.) 

One  may  destroy  the  cerebrum  only  in  an  animal  and 
thus  leave  the  medullary  centers  intact.  This  is  easiest 
done  in  a  cat.  Normal  respiration  may  go  on  (no  further 
anesthetic  is  needed)  and  the  blood-pressure  remains  high. 


206 


expekimejSttal  pharmacology 


EXPERIMENT  XXX. 

Heroine  or  Codeine.     (Spinal  Bog:    Blood-pressure,  Lung 
Volume  and  Bladder  Contractions.) 

1.  Examine  carefully  the  apparatus  shown  in  Figs.  197 
and  198.    Arrange  a  dog  (ten  or  twelve  kilos)  for  record- 


Fig.  197. — Mercury  bulb. 

ing  blood-pressure.  The  injecting  burettes  contain  heroine 
(one  cubic  centimeter  equals  five  milligrams)  and  adrena- 
line (1:10,000).    Arrange  for  artificial  respiration. 

Open  the  abdomen  and  pick  up  the  bladder.    Insert  into 
it  at  the  urachus  a  glass  tube  connected  with  a  mercury 


PRELIMIISTARY    OPERATIONS 


207 


bulb.  (See  Figs.  198  and  199  for  technic  and  apparatus; 
also  see  Experiment  XXVIII,  page  189.)  Use  a  large 
bowled  tambour  to  record  the  bladder  contractions.  If  the 
bladder  is  full  of  urine  do  not  allow  more  of  this  to  escape 
than  can  be  avoided.  Arrange  the  mercury  bulb  as  shown 
in  Fig.  199  and  fill  the  bulb  about  two-thirds  full  of  warm 
salt  solution.  Insert  the  cork  which  carries  a  glass  tube 
to  connect  with  the  tambour.  It  is  best  not  to  connect  the 
tambour  tube  until  the  lung  shield  is  inserted  and  the  dog 


flercury  bulb 
zso  c.c. 

Salt  solution 


Class  or  wefal  tube 

qrooved  where  tied 

into  bladder  wall. 


Abdominal  wall 


Fig.     198. — Arrangement    of    apparatus    for    recording    bladder    contractions.       A     catheter 
passed  through  the  urethra  may  also  be  used  sometimes  to  connect  to  the  mercury  bulb. 

is  pithed,  as  the  bladder  tambour  and  tube  would  be  in 
the  way  of  the  operation.  Place  a  hemostat  on  the  penis 
or  vulva  of  the  animal  to  prevent  urination. 

By  a  median  longitudinal  incision  open  the  thorax  (start 
artificial  respiration  at  once)  and  expose  the  right  lung 
and  the  heart  (do  not  open  the  pericardium).  The  anterior 
mediastinum  should,  if  possible,  be  gently  turned  over  to 
the  left.    Pick  vp  both  phrenic  nerves  and  cut  them.    Whiff 


208 


EXPERIMEISTTAL   PHARMACOLOGY 


The  lung  shield  (Fig.  200)  should  be  dipped  in  warm  Avater 
and  inserted  in  the  chest  in  such  a  manner  that  the  large 
notch  at  the  lower  border  of  the  shield  will  just  pass  over 
the  pedicle  and  vessels  of  the  right  lung.  The  flanged 
portion  which  turns  outward  at  the  right  hand  end  of  the 
shield  rests  on  the  anterior  surface  of  the  diaphragm. 
There  is  a  groove  in  the  shield  between  the  large  notch  and 
the  out-turned  flange.    This  groove  is  for  the  passage  (me- 


Fig.  199. — The  forefinger  is  placed  over  the  inguinal  region  just  at  the  lower  edge 
of  the  abdomen.  The  beating  of  the  femoral  artery  should  be  felt  just  beneath.  An  in- 
cision should  be  made  just  over  the  area.  Note  the  little  fold  of  skin  picked  up  by  the 
forceps  while  the  scissors  are  used  to  cut  away  the  skin  and  fascia.  Do  not  use  a 
scalpel  here.  The  arrangement  of  the  mercury  bulb  for  recording  bladder  contractions 
is  also   shown. 


sially)  of  the  inferior  vena  cava.  This  must  not  be  closed 
off  or  the  dog  will  die.  Now  cut  a  small  hole  in  the  skin 
of  the  right  side  about  the  position  of  the  anterior  border 
of  the  sixth  intercostal  space.  Pass  an  aneurism  needle 
through  the  muscular  wall  (through  the  skin  incision)  and 
into  the  chest.    Be  sure  the  'parietal  pleura  does  not  peel 


ADJUSTMENT  OF  LUNG  SHIELD 


209 


of  and  keep  the  aneurism  needle  from  entering  the  chest 
cavity  proper.  Beside  this  aneurism  needle  insert  another 
in  the  same  opening  and  pnll  the  sides  of  the  opening  thus 
made  far  enough  apart  to  insert  the  bent  end  of  the  glass 
tube  sho\^^l  in  Fig.  201.  Be  sure  the  pleura  does  not  close 
the  inner  end  of  the  tube.  This  is  the  most  common  source 
of  failure  in  this  experiment.  The  edge  of  the  lung  may 
also  move  up  when  inflated  and  close  the  tube.  Watch  this. 
With  hemostats  clamp  the  glass  tube  (catching  the 
strings)  air-tight  in  the  chest  wall.     Now  close  the  chest 


Fig.  200. — Lung  shield  made  of  thin  sheet  brass  with  a  wire  rim  soldered  around 
the  edge  to  add  strength.  A  little  more  than  one-half  natural  size.  The  large  notch 
passes  down  over  the  pedicle  of  the  right  lung.  To  the  right  of  the  large  notch  is  seen 
a  grooved  chapnel  for  the  passage  (mesially)  of  the  inferior  vena  cava.  (For  method 
of  use  see  text.) 


and  fasten  it  air-tight  either  with  hemostats  or  b}^  sewing. 
Connect  the  glass  tube  to  a  large  bowled  recording  tam- 
bour. This  records  the  lung  volume  changes.  The  record 
should  be  about  titw  to  three  inches  high.  The  adjustable 
by-pass  may  be  opened  to  allow  excess  air  (which  the  tam- 
bour can't  hold)  to  escape.  (Air  also  Avill  then  enter  the 
by-pass  again  when  the  lungs  collapse.  This  exchange  is 
approximately  constant,  hoAvever,  with  regular  artificial 
respiration  and  will  not  interfere  with  the  validity  of  the 


210 


EXPEEIMENTAL   PHAEMACOLOGY 


record.)     The  animal  should  be  firml}^  tied  down  to  the 
operating  board  so  the  chest  cannot  move  too  much. 

Now  pass  ligatures  through  the  sides  of  the  neck  as  de- 
scribed in  Experiment  XXIX,  page  195  (see  also  Experi- 
ment XXVIII,  2,  page  192  and  Figs.  183  and  184).  Isolate 
the  left  carotid  artery  and  arrange  to  inject  chloroform 
(one  or  two  cubic  centimeters)  into  it.  Proceed  as  in  Ex- 
periment XXIX  to  destroy  the  animal's  brain,  but  try  to 


Class  tube 


ijb  recording  tambour 

Hemost^t  clamping  string 
K    on  corK  to  chesT^ 


Adjustable 
(By-paJJ. 


Fig.  201. — Arrangement  of  apparatus  for  recording  the  volume  changes  of  the  right 
lung  by  use  of  the  lung  shield.  The  glass  tube  shown  in  the  upper  part  of  the  illustra- 
tion, has  its  bent  end  passed  into  the  chest  cavity. 

do  this  by  injecting  the  chloroform  into  the  left  carotid 
artery  alone.  If  you  succeed  Avell  in  this  you  can  avoid 
dissecting  out  the  right  vertebral  artery.  The  blood-pres- 
sure should  come  down  at  least  to  a  height  of  one  or  one 
and  one-half  inches  above  the  base  line  as  seen  on  the  drum. 
If  the  pressure  does  not  fall,  or  even  goes  up  higher,  the 
injection  has  not  succeeded.     A  very  high  pressure  thus 


ACTIOX   OF    OPIUM  ALKALOIDS  2.11 

produced  may  last  for  some  time  and  is  very  liable  to  cause 
the  lieart  to  stop  (possibly  from  the  extra  strain).  The  re- 
spiratory movements  of  the  dog  should  stop  entirely.  If 
they  do  not,  wait  a  little  while  and  make  a  second  chloro- 
form injection.  Sometimes  the  diaphragm  will  contract 
at  every  beat  of  the  heart.  This  is  due  to  an  action  cur- 
rent generated  by  the  lieart  Avhere  the  phrenics  pass  over 
it.  These  nerves  should  therefore  be  cut  heUveen  the  heart 
and  the  diaphragm  (while  the  chest  is  open). 

The  animal  should  now  lie  cpiietly  and  the  blood-pressure 
should  be  about  one  inch  or  a  little  less  above  the  base  line 
on  the  drum.  Just  above  the  blood-pressure  should  be  the 
lung  volume  record  (about  two  or  three  inches  in  height), 
and  above  this  about  one-fourth  inch  should  be  placed  the 
tambour  record  for  the  bladder  which  is  now  connected  up 
to  the  mercury  bulb.  Take  about  one  inch  of  normal  trac- 
ing. If  everything  is  satisfactory  then  inject  five  cubic 
centimeters  of  heroine  (or  codeine)  solution.  Is  there  any 
change  in  the  bladder  f  If  not  it  may  have  been  completely 
empty  and  contracted  before  the  drug  was  injected.-  Do 
you  get  any  lung  volume  change!  How  do  you  account 
for  this?  What  mechanical  factors  are  involved?  How 
does  positive  artificial  respiration  differ  from  natural  res- 
piration ?  As  soon  as  you  get  a  well  marked  action  from 
the  drug  injected,  then  run  into  the  vein  one  cubic  centi- 
meter of  adrenaline.  How  does  this  affect  your  record? 
How  do  you  account  for  this  ?  Of  what  clinical  use  might 
this  be?  AVhat  effect  does  this  have  on  the  bladder?  How 
do  you  explain  this? 

Wait  until  the  records  return  to  normal  and  then  inject 
eight  cubic  centimeters  of  the  second  alkaloid  (codeine 
or  heroine,  or  vice  versa,  depending  on  which  drug  was  in- 
jected the  first  time).  How  does  this  drug  affect  the  blad- 
der and  lungs?  The  dose  is  larger  than  the  first  one  given. 
How  do  these  doses  compare  with  those  given  to  dogs  to 
narcotize  them  before  operations?    Has  the  first  injection 


212 


EXPEEIMEXTAJL   PHAR]MACOLOGT 


ill  -^^^''^SfcU^  ay*ul  Cf/tdi 


destroyed.      The    tracing    v/a^    ~a- 


ronchioles)   and  blood-pressure 

_;      .;.      Both   brain    and  cord   were 

le    rrethol    described    in    Experiment    LXX. 


ACTIOX    OF    OPIUM  .\J.KALOID^ 


213 


Fig.  203.— Tracing  si 


o-.vi!ig  ihe  action  of  codeine  and  "epinine-  on  the  bladder,  bronchioles 
and  blood-pressure  in  a  pithed   dog.  ""i-uioics 


214 


EXPERIMENTAL   PHARMACOLOGY 


SlladdM.CcyMa^^^>^. 


Q^^itoXuj-M. . 


■r" 


r         ^-'^     ,iiiJl 


Fig.  204. 


-Tracing  showing  the  action  of  muscarine   (and  "epinine")   in  a  pithed  dog  alter 
the   animal    had    become    irresponsive    to    codeine    injections. 


ACTION   OF    OPIUM   ALKALOIDS 


215 


p  2.  •  " 

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216 


EXPERIMEJ^TAL    PHARMACOLOGY 


caused  any  permanent  change  in  the  kings  or  bladder  that 
you  can  detect  by  the  results  of  your  second  injection? 
Give  more  adrenaline  to  revive  the  animal.  Do  you  see 
the  reflected  effects  of  the  filling  and  emptying  of  the  heart 


Glass  catheter 
Metal  catheter 

Fig.   206. — Three  kinds   of  catheters. 

in  your  lung  tracing?'  Stop  the  artificial  respiration  for  a 
few  seconds  and  watch  for  the  heart  action  to  affect  the 
lung  tracing. 


Fig.  207. — Dissection  showing  the  position  and  relation  of  the  organs  and  struc- 
tures witliin  the  lower  pelvis  (dog).  The  pubes  were  sawed  apart  and  the  left  side  of 
the  bone  shows  at  L.S.P.  A,  probe  passed  into  the  urethra,  Ur;  B,  probe  passed  in  the 
vagina,  V;  R.S.P.,  right  edge  of  the  (divided)  symphasis  pubis;  V,  vulva;  F.C.,  fossa 
clittoridis;  Ci,  clittoris;  IV. V.,  vaginal  wall;  Bl,  bladder;  R.U.,  right  ureter  entering  the 
bladder;  R,   rectum;    Ut,  uterus. 


ACTION"  OF  STRYCHNINE  217 

The  animal  will  probably  be  very  low  by  this  time.  If 
it  is  still  alive  and  the  pressure  is  high  enough  inject  some 
other  of  the  opium  alkaloids,  such  as  dionine,  thel)aine  or 
peronine,  and  try  to  counteract  this  effect  by  injecting 
''epinine"  (1:1000 — Burroughs,  Wellcome  and  Company, 
New  York).  "Epinine"  is  nearly  related  chemically  and 
pharmacologically  to  adrenaline. 

2.  After  the  animal  dies,  if  it  is  a  female,  try  to  pass  a 
catheter  (Fig.  206)  through  the  urethra  into  the  bladder. 
Consult  Fig.  207  to  do  this.  A  catheter  made  of  a  very 
small  glass  tube  slightly  curved  at  the  end  is  very  satis- 
factory for  this  purpose.  Could  you  thus  pass  a  catheter 
in  a  living  animal?  Isolate  the  left  kidney  (or  the  spleen) 
and  place  it  in  an  oncometer.  Place  a  loop  of  intestine  in 
an  oncometer  (see  Fig.  157). 

EXPERIMENT  XXXI. 

Strychnine.    (Frog:   Action  on  the  Cord.) 

1.  Pith  a  frog  and  attach  it  to  a  frog  board.  Dissect 
loose  the  right  tendo  Achillis  and  gastrocnemius  muscle 
but  do  not  injure  the  tissues  of  the  thigh.  Cut  the  tendo 
Achillis  long  and  drive  a  carpet  tack  through  the  knee  joint 
region  (avoid  the  artery  and  sciatic  nerve)  as  shoAvn  in 
Fig.  208.  The  tack  gives  a  firm  point  of  attachment  for 
the  gastrocnemius  muscle.  Then  place  the  frog  board  in 
a  large  clamp  and  arrange  all  apparatus  as  shown  in  the 
illustration.  The  drum  should  have  a  fairly  rapid  speed 
and  the  muscle  lever  should  write  near  the  bottom  of  the 
drum  (leaving  enough  space  below  for  the  time  record). 
With  a  hypodermic  needle  inject  into  the  dorsal  lymph  sac 
of  the  frog  one  cubic  centimeter  of  strychnine  sulphate 
solution  (one  cubic  centimeter  equals  one-half  inilligram). 
Wait  about  three  minutes  for  the  drug  to  be  absorbed  and 
then  start  the  drum.     The  frog  will  soon  show  a  marked 


218 


EXPERIMENTAL   PHARMACOLOGY 


reaction  and  it  is  important  to  record  the  first  manifesta- 
tions of  this  effect.  The  drum  is  kept  running  and  pres- 
ently further  results  will  be  obtained.  When  the  first 
round  is  completed  lower  the  drum  and  take  a  second 
round.  Blow  against  the  frog  and  note  the  results.  How 
do  the  contractions  obtained  on  the  first  round  compare 
with  those  of  the  second?    After  the  two  rounds  are  com- 


Fig.     208. — Arrangement     of    frog    and     apparatus    for     recording    the     contractions     of 
the   gastrocnemius   muscle    during   convulsions.      The    animal's   brain   is   destroyed. 


pleted  dissect  out  the  sciatic  nerve  on  the  back  of  the  right 
thigh  (see  Fig.  47,  page  54)  and  cut  the  nerve  in  two. 
Now  stimulate  the  frog  (blow  against  it)  and  note  the  re- 
sults on  your  records.  What  does  this  show?  What  can 
you  say  regarding  the  action  of  strychnine?  Pass  a  soft 
copper  wire  down  the  spinal  canal  and  destroy  the  cord. 


ACTION    OF    STRYCHNINE 


219 


What  effect  has  this  on  the  convulsions!  Can  you  locate 
the  seat  of  action  of  the  drug  from  this  experiment?  In 
what  other  ways  might  you  test  out  your  conclusions ''. 


jStufO^tti'^^. 


*>  ■>S<,tovu)Lt . 


Fig.    209. — Tracing    showing   the    action    of    strychnine    on    the    trog    made    by 
tions   of  the  gastrocnemius   muscle  as  arranged   in   Fig.   308. 


the    coatr; 


This  is  the  usual  method  for  obtaining  graphic  records  to 
illustrate  the  action  of  convulsant  poisons.  This  action  can 
usually  be  shown  quite  well  on  frogs,  and  since  frogs  are 
cheaper  and  more  easily  managed  than  mammals,  they  are 
generally  used  for  this  purpose.    The  cerebrum  is  destroyed. 


220  EXPERIMENTAL   PHARMACOLOGY 

EXPERIMENT  XXXII. 

Strychnine.     (Frog:     Heart  and  Vago-sympathetic 

Nerve.) 

1.  3Pitli  a  frog  and  destroy  the  spinal  cord  with  a  soft 
copper  wire.  Examine  the  beating  of  the  lymph  hearts 
(see  Fig.  66)  before  and  after  the  cord  is  destroyed.  How 
is  the  beat  of  these  affected!  Fasten  the  frog  down,  ven- 
tral side  upward,  and  dissect  out  the  vagus  nerve  (Fig.  60). 
Arrange  to  record  heart  tracings  on  a  m,oderately  slow 
drum  (Fig.  63).  Take  about  one  inch  of  normal  tracing 
and  then  stimulate  the  vago-sympathetic  nerve  and  record 
the  inhibition  and  recovery.  Take  two  inches  more  of  the 
normal  record  and  repeat  the  stimulation.  Lower  the 
drum  and  start  a  second  round.  Drop  on  to  the  heart  a 
few  drops  of  strychnine  sulphate  solution  (one  cubic  centi- 
meter equals  one-half  milligram)  and  after  a  feAV  seconds 
again  stimulate  the  nerve.  Thic  stimulation  record  should 
be  directly  above  the  first  inhibition  record  in  the  first 
round  on  the  drum.  Appl}^  more  drug  to  the  heart  and 
stimulate  again.  Be  sure  the  stimulating  current  is  not 
too  strong  and  do  not  continue  its  application  to  the  nerve 
any  longer  than  is  absolutely  necessary  or  the  nerve  (or 
its  endings)  may  be  affected.  Apply  more  drug  and  then 
stimulate  again.  How  is  the  beat  of  the  heart  affected? 
Is  the  muscle  of  the  heart  directly  concerned  in  this  1  "What 
are  the  later  effects  of  strychnine  on  the  heart  when  thus 
applied?  How  does  strychnine  affect  the  innervation  of 
the  frog's  heart? 

EXPERIMENT  XXXIII. 
Strychnine.     (Turtle:     Heart  and  Vagus  Nerve.) 

1.  Pith  a  turtle  and  fully  destroy  the  cord  by  pushing 
a  soft  copper  or  iron  wire  (No.  14  or  16)  down  the  spinal 


ACTION    OF    STRYCHNINE     ^ 


221 


canal.  Arraiift-e  for  takino-  heart  tracings.  Dissect  out 
the  vagus  nerve  in  the  neck  (Fig.  70)  and  record  a  nor- 
mal inhibition  at  two  places  in  the  lower  round  on  the 
drum.  Lower  the  drum  and  start  a  second  round.  Apply 
strychnine  solution  (one  cubic  centimeter  equals  one  milli- 


Fig.    210. — Gi-eene's    method    of    irrigating   the    heart. 

gram)  to  the  heart  with  a  medicine  dropper  or  according 
to  Greene's  method  (Fig.  210)  for  irrigating  the  lieart.  Do 
you  notice  any  inmiediate  change  in  the  appearance  of  the 
heart  beat?  Might  this  be  due  simply  to  the  fluid  moisten- 
ing the  heart  muscle  (as  normal  salt  solution  would  do)  or 


222 


EXPERIMENTAL   PHARMACOLOGY 


to  temperature  changes  caused  by  applying  the  solution? 
How  could  you  avoid  these  possible  effects?  Stimulate 
the  vagus  nerve  again  and  record  the  results.  What  do 
you  observe!  Apply  more  drug  (the  record  is  made  as  in 
Experiment  XXXII)  and  try  stimulating  the  nerve  from 
time  to  time.     Are  any  changes  observed?     How  do  you 


Fig.  211. — Tracing  from  the  heart  of  a  turtle  showing  the  action  of  strychnine.  At 
the  short  bar  the  vagus  trunk  was  stimulated  and  stopped  the  heart  for  a  brief  period. 
Subsequently  a  solution  of  strychnine  was  dropped  on  the  heart  (at  X).  The  rate  of 
beat  was  apparently  slightly  accelerated.  Later  (at  R.J\S.)  the  vagus  trunk  was  again 
stimulated  but  could  not  slow  or  stop  the  heart.  What  structures  were  affected  by  the 
drug? 

account  for  this?  How  does  this  compare  with  the  re- 
sults obtained  by  other  students?  Did  the  turtle  have  any 
convulsions?    How  do  you  explain  this? 


EXPERIMENT  XXXIV. 


Strychnine.     (Dog:    Blood-pressure,  Respiration,  and 
Kidney,  Spleen  or  Intestinal  Loop.) 

1.  Arrange  a  dog  for  taking  blood-pressure,  respiration, 
and  an  oncometer  tracing  of  either  the  spleen,  left  kidney 


ACTION    OF    STRYCH2sriNE 


2-:>?> 


or  a  small  loop  of  the  intestine.  For  the  latter  record  an 
instrument  similar  to  the  one  shown  in  Fig.  212  may  be 
nsed,  or  the  ointment  box  kidney  oncometer  (Fig.  157) 
may  be  employed.  It  is  necessary  not  to  get  too  large  a 
loop  of  intestine  into  the  oncometer.  Three  inches  of  the 
small  intestine  bent  into  a  small  loop  is  sufficient.  It  is 
very  desirable  to  fasten  safety-pins  through  the  ends  of 
the  loop  as  shown  in  Fig.  212  to  prevent  more  of  the  in- 
testine from  Avorking  into  the  oncometer  after  the  experi- 


Pin  +0  fas-ten 
loop  of  InfesHne 


Openinq  to  receive  loop 
of  intestine 


Fig.  212. — Glass  oncometer  for  a  small  loop  of  the  intestine.  The  safety  pins 
should  be  passed  through  the  edges  of  the  wall  of  the  intestine  to  prevent  more  of  the 
intestine  from  working  into  the  oncometer  or  any  part  of  the  loop  from  getting  out. 
About  three-fourths  natural  size. 


ment  has  started.  This  may  also  be  accomplished  by  scav- 
ing  a  stitch  through  each  end  of  the  loop  with  a  needle  and' 
thread  and  tying  the  thread  in  the  small  holes  of  the  onco- 
meter. If  the  gut  is  allowed  to  keep  craAvling  more  and 
more  into  the  instrument  as  the  experiment  goes  on  the 
records  Avill  soon  be  spoiled.  When  the  oncometer  is  ad- 
justed then  attach  the  tube  for  the  recording  tambour  and 
close  the  ahdo7nen  securely  Avith   hemostats   or   stitches. 


224  EXPEEIMENTAL   PHARMACOLOGY 

Why  is  this  so  important?  The  injecting  bnrettes  contain 
adrenaline  and  strj^chnine  sulphate  (one  cubic  centimeter 
equals  one-half  milligram). 

Adjust  all  writing  points  (so  they  will  pass  each  other) 
on  the  drum.  Keep  the  anesthesia  moderately  deep  and 
as  even  as  possible.  The  oncometer  tracing  should  be  the 
upper  record,  the  blood-pressure  next  below,  then  the  res- 
piration, and  at  the  bottom  of  the  drum  should  be  the  base 
line  and  time  marker.  The  student  (and  the  instructor) 
should  make  careful  observations  in  each  experiment  to 
determine  about  what  sized  tambour  bowls  and  what  mag- 
nification should  be  used  for  each  organ  from  which  rec- 
ords are  obtained.  This  will  necessarily  vary  largely  with 
different  types  of  tambours  and  must  be  determined  in 
each  laboratory  from  experience. 

Take  about  one  inch  of  satisfactory  tracings  and  then 
inject  one  cubic  centimeter  of  strychnine.  What  is  the 
result?  Note  the  time  of  day.  After  the  pointers  return 
to  normal  (which  should  be  in  a  short  time)  inject  one 
cubic  centimeter  of  strychnine  again.  When  the  records  are 
again  back  to  normal  inject  one-half  cubic  centimeter  of 
adrenaline.  Do  you  get  satisfactory  records?  What  is 
the  action  of  small  (therapeutic)  doses  of  strychnine  on 
the  heart  and  circulation!  Slowly,  from  time  to  time,  in- 
ject one  cubic  centimeter  doses  of  strychnine  and  allow 
the  animal  to  lie  perfectly  quietly.  Is  there  any  change  in 
the  blood-pressure  as  the  action  of  the  drug  comes  on 
slowly!  After  a  time  there  will  be  a  sudden  reaction.  Be 
sure  the  drum  is  going  and  that  3^ou  record  the  result  well. 
Do  not  give  any  more  drug  for  a  while  then  and  wait  for 
further  developments.  How  is  the  oncometer  record  af- 
fected? How  do  3^ou  account  for  this?  Be  sure  you  are 
ready  to  give  artificial  respiration  if  it  is  needed.  Observe 
carefully  the  actions  of  the  face  and  mouth  muscles  when 
the  animal  shows  most  marked  symptoms.  What  is  meant 
by  the  expression  " risiis  sardonicits"?    Are  there  any  spe- 


ACTION    OF    STRYCHXIXE  225 

cial  pupillary  changes?  Do  yon  get  any  results  resembling 
a  Clieyne-Stokes  respiration?  Deepen  the  anesthesia  a 
little  and  see  if  you  can  depress  the  action  of  the  drug  a 
little.  Try  touching  the  animal  from  time  to  time  or  jar 
the  board  a  little  and  note  the  effect.  What  parts  of  the 
central  nervous  system  are  mainly  atfected?  What  is  the 
difference  between  epileptiform,  clonic  and  tonic  convul- 
sions? How  do  you  explain  these?  How^  long  did  it  take 
for  the  action  of  the  drug  to  come  on?  Do  you  get  satis- 
factory oncometer  tracings?  What  mechanical  factors  are 
concerned  in  the  production  of  these?  Your  apparatus 
should  be  carefully  arranged  so  you  can  hold  the  stands, 
etc.,  do^^Tl  firmly  on  the  table  to  prevent  them  from  being 
shaken  out  of  place. 


Fig.  213. — Glass  ureteral  cannula  with  rubber  tube  connection.     About  one-half  natural  size. 

Inject  some  adrenaline  into  the  vein.  How  does  this 
affect  the  animal?  Secure  records  of  as  many  typical 
convulsions  as  you  can.  Many  of  these  will  probably  be 
spoiled  by  movements  of  the  apparatus.  Crowd  on  enough 
ether  to  check  the  convulsions,  then  open  the  bladder  and 
insert  a  cannula  (or  pass  a  catheter  if  you  can)  and  close 
the  abdomen  firmly  with  hemostats.  Draw  off  some  urine 
and  test  it  for  reducing  substances.  A^liat  action  will 
strychnine  have  on  the  glycogen  stores  of  the  body?  How 
is  this  brought  about?  What  mechanisms  are  concerned? 
How  is  strychnine  excreted?  Could  you  get  a  positive  test 
for  it  in  the  urine?  How  long  does  the  drug  remain  in 
the  body  before  it  is  excreted?  What  bearing  does  this 
have  on  the  treatment  of  strychnine  poisoning? 


226  EXPERIMENTAL   PHARMACOLOGY 

Kill  the  animal  by  a  large  dose  of  the  drug.  What  is 
the  immediate  cause  of  death? 

If  time  permits  open  the  abdomen  and  dissect  out  both 
ureters  (Fig.  162)  and  trace  their  course  to  the  bladder. 
Could  you  tie  a  cannula  (Fig.  213)  in  each  ureter  and  col- 
lect the  urine  from  each  kidney  seiDarately?  What  is  the 
innervation  of  the  ureters'? 

EXPERIMENT  XXXV. 

Strychnine.     (Ether,  Morphine,  Chloral  Hydrate.)    (Dog: 

Blood-pressure,  Respiration,  Oxygen  Consumption, 

Air  Embolism.) 

1.  Read  over  carefully  the  section  on  oxygen  consump- 
tion given  in  Experiment  XXVITI,  page  177.  The  ap- 
paratus there  used  is  of  a  very  simple  form  and  will  be 
available  in  most  laboratories.  A  better  but  somewhat 
more  complicated  form  is  shown  in  Fig.  172.  This  figure 
shows  in  addition  a  special  arrangement  for  measuring 
the  oxygen  each  time  it  is  run  in.  If  only  enough  water  be 
placed  in  the  pressure  bottle  to  allow  200  or  300  cubic 
centimeters  (the  bottom  of  the  bottle  must  first  be  filled  up 
to  the  level  of  the  spout)  to  run  down  into  the  graduated 
cylinder  at  a  time,  then  the  measuring  of  this  amount  of 
oxygen  before  it  is  run  into  the  pan  becomes  automatic 
and  can  quickly  be  done  each  time.  If  the  oxygen  tank 
be  opened  a  little  oxygen  will  be  forced  through  the 
T-tube  into  the  graduated  cylinder.  This  oxygen  is  un- 
der pressure  and  will  drive  the  water  in  the  cylinder  up 
into  the  pressure  bottle.  If  it  is  especially  desired  for 
greater  accuracy,  the  bottle  can  then  be  lowered  to  the 
level  of  the  graduated  cylinder  to  avoid  compression  of 
the  oxygen  Mdiile  its  volume  is  being  measured,  but  this 
is  not  generally  necessary,  for  the  compression  of  the 
oxygen  in  the  graduated  cylinder  by  the  colunm  of  water 
up  to  the  pressure  bottle  will  be  the  same  each  time  and 


ACTION  OF  MORPHINE   ON  OXYGEN  CONSUMPTION  ^'11 

will  thus  not  cliaiige  separate  readings  on  the  drum.  This 
automatic  measuring  of  the  oxygen  saves  time  and  should 
be  done  by  the  student  who  manages  the  apparatus  on 
the  drum.  The  measuring  device  can  also  be  used  on  the 
simple  apparatus  shoAvn  for  Experiment  XXVIII  if  de- 
sired. 

Several  very  interesting  and  important  actions  of  cer- 
tain drugs  can  be  recorded  either  with  the  apparatus 
shown  in  Fig.  172  or  with  that  illustrated  in  Fig.  175. 
Thus  the  short,  rapid,  up-and-down  movements  of  the  heart 
lever  records  the  respiration  of  the  animal  even  more  ac- 
curately than  does  the  stethograph  around  the  body.  In 
addition  the  actual  relative  amount  of  gases  passing  in 
and  out  of  the  lungs  at  any  given  period  can  be  compared. 
And  any  general  change  in  the  volume  of  the  lung  con- 
tents (contraction  or  relaxation  of  the  bronchioles)  is 
w^ell  shown.  For  the  latter  purpose  the  short  respiratory 
excursions  of  the-  heart  lever  on  the  drum  should  be  mag- 
nified to  write  about  one  or  one  and  one-half  inches  in 
amplitude. 

Arrange  a  medium  sized  dog  for  recording  blood-pres- 
sure and  respiration.  The  injecting  burettes  contain 
adrenaline  and  morphine  (one  cubic  centimeter  equals 
five  milligrams).  Attach  the  apparatus  for  recording 
oxygen  consumption  and  take  a  normal  record.  This  will 
involve  at  least  one  (and  better  two  or  three)  complete 
notches  on  the  oxygen  record.  Now  deepen  the  ether  anes- 
thesia a  little  [not  too  much)  and  see  if  this  slows  down 
the  oxygen  consumption.  What  Avould  you  expect  the 
ether  to  do?  Now  get  the  animal  into  a  perfectly  satis- 
factory condition  and  inject  three  cubic  centimeters  of  mor- 
phine. How  does  this  affect  the  oxygen  record?  Can  you 
determine  whether  the  observed  result  is  due  to  a  central 
or  to  a  peripheral  action  of  the  drug?  Are  there  any  evi- 
dences of  bronchial  changes!     Explain.     Inject  one  cubic 


228 


EXPERIMENTAL   PHARMACOLOGY 


Fig.  214. — Tracing  showing  the  action  of  morphine  (and  adrenaline)  on  the  rate 
of  oxygen  consumption,  on  the  bronchioles,  respiration  and  blood-pressure  in  a  dog. 
At  the  point  marked  "bronch.  contract."  in  the  upper  record  it  will  be  seen  that  the 
curve  actually  turns  downward  for  a  short  distance.  This  is  due  to  the  marked  con- 
traction of  the  bronchioles  forcing  a  part  of  the  supplemental  (or  reserve)  air  out  of  the 
lungs.  This  is  probably  also  reflected  on  the  respiratory  tracing  by  limiting  the  expan- 
sion of  the  chest.  Adrenaline  counteracts  this  broncho-constricting  action  of  morphine 
and  the  three  injections  of  adrenaline  each  causes  a  marked  increase  in  the  depth  of 
respiration  which  lasts  approximately  during  the  period  that  the  action  of  the  adrenaline 
can  be  seen  on  the  blood-pressure.  Experimentally  it  has  been  shown  by  Guber  at 
Zurich  that  animals  poisoned  by  a  minimal  fatal  dose  of  morphine  recover  if  they  be  in- 
jected with  adrenaline.  How  would  you  explain  the  prevention  of  death  (from  the 
morphine)    in  these  cases  by  adrenaline? 


ACTION  OF  STRYCHNINE  ON   OXYGEN  CONSUMPTION        229 

centimeter  of  adrenaline.  How  does  tliis  affect  the  record  ? 
Now  give  a  second  dose  (three  cubic  centimeters)  of  mor- 
phine and  see  what  effect  this  has  on  the  rate  of  oxygen 
consmiiption.  Take  three  or  four  notches  in  the  oxygen 
record  to  get  the  prolonged  effects  of  the  drug. 

Now  arrange  for  all  the  drum  space  you  can  command 
and  prepare  to  record  the  rate  of  oxygen  consumption 
after  strychnine.  It  is  to  he  recalled  that  the  CO2  exhaled 
by  the  animal  may  vary  quite  as  much  as  the  rate  of  oxy- 
gen consumption  for  short  periods  of  time.  If  a  consider- 
able excess  of  CO2  is  excreted  it  can  affect  the  record 
somewhat  before  it  is  absorbed.  Will  this  mean  a  pro- 
longation or  a  shortening  of  the  oxygen  record?  Will  it 
add  to  or  subtract  from  the  relative  length  of  time  which 
a  given  injection  of  oxygen  will  last?  Consider  this  point 
carefully  in  observing  the  manner  in  which  strychnine 
acts  on  the  metabolism. 

Arrange  all  writing  points  and  inject  one  cubic  centi- 
meter of  strychnine  (one  cubic  centimeter  equals  one-half 
milligram).  Wait  a  little  and  then  repeat  the  injection 
(one  cubic  centimeter).  Continue  this  at  brief  intervals, 
recording  carefully  the  rate  of  oxygen  consumption  all 
the  time.  Be  sure  the  animal  cannot  shake  down  your 
apparatus  when  the  convulsions  come  on.  Continue  giv- 
ing strychnine  until  convulsions  are  fully  developed.  How 
do  these  affect  the  rate  of  oxygen  consumption  ?  What  be- 
comes of  the  oxygen  taken  up  by  the  animal  ?  What  is  the 
respiratory  quotient?  How  is  it  determined?  Examine 
the  pupils  during  and  after  a  convulsion.  What  do  you 
observe?  Crowd  on  ether  and  see  if  you  can  stop  the 
convulsions.  How  does  this  now  affect  the  oxygen  con- 
sumption! Lighten  the  anesthesia  and  empty  the  strych- 
nine out  of  the  burette.  Fill  the  burette  with  chloral  hy- 
drate solution  (four  per  cent)  and  then  just  after  a  con- 
vulsion inject  one  cubic  centimeter  of  the  solution.     How 


230  EXPERIMENTAL   PHARMACOLOGY 

does  this  affect  the  convulsions,  blood-pressure,  respiration 
and  oxygen  consumption?  Inject  more  chloral  from  time 
to  time  and  observe  its  general  action  as  fully  as  you  can. 
If  the  animal  is  still  alive  empty  the  chloral  out  of  the 
burette,  then  take  the  burette  out  of  the  clamp  and  place 
the  upper  end  of  the  empty  burette  in  your  mouth.  Take 
the  bull-dog  off  the  femoral  vein  and  blow  some  air  into 
the  vein.  Replace  the  bull  dog  and  watch  the  action  of 
the  air  on  the  animal.  What  is  meant  by  air  embolism! 
How  may  it  be  produced!  How  does  it  act  inside  the 
heart  chambers!  In  the  vessels!  Blow  more  air  into 
the  vein  if  necessary  to  kill  the  animal.  What  conclu- 
sions can  you  draw  from  this! 

Caution. — The  alimentary  canal  of  the  dog  contains  large  numbers  of  tape 
worms  and  their  eggs.  If  these  eggs  are  swallowed  by  other  animals  infection 
may  occur. 

If  time  permits,  dissect  out  the  nerves  to  the  bladder 
(and  uterus  if  the  animal  is  a  female). 

EXPERIMENT  XXXVI. 
Strychnine.     (Student:    Reaction  Time.) 

1.  Test  the  acuteness  of  hearing  of  the  student  who  is 
to  act  as  the  subject  of  the  experiment.  Do  this  by  allow- 
ing the  student  to  sit  at  a  table  (at  complete  rest)  with  his 
ear  or  the  side  of  his  head  against  a  heavy  stand  (which 
must  not  be  moved  later).  A  watch  is  now  moved  away 
from  the  ear  of  the  subject  until  the  ticking  can  just  be 
heard  (note  the  position  of  the  watch,  i.e.,  which  side  is 
toward  the  subject).  Mark  this  distance  on  the  table  or 
otherwise  and  then  take  the  watch  back  to  the  point 
where  the  ticking  just  fails  to  be  heard.    Mark  this  point. 

2.  Now  refer  to  the  arrangement  of  the  apparatus 
shown  in  Figs.  134  and  137  (also  see  Experiment  XIII,  1, 


STRYCHNINE   AND    PIC'ROTOXINE 


231 


page  144)  and  record  tlie  snhjeet's  normal  reaction  time 
for  sight,  toncli  and  sound. 

•  3.  Take  two  tubes  of  oil  (or  water  color)  paint,  one 
white,  the  other  red  (other  colors  may  also  be  used),  and 
with  a  brush  on  a  white  tile  surface  (pill  tile)  make  a  series 
of  mixtures  of  white  and  red  varying  only  the  slightest 
degree  in  color.  Also  make  several  just  alike.  Number 
these  and  let  the  subject  note  all  those  between  which  he 
can  just  distinguish  a  difference.     Eecord  these  results. 

4.  Now  let  the  subject  take  a  therapeutic  dose  of 
strychnine. 

Caution. — Strychnine  is  very  poisonous.  The  average  dose  is  one-sixtieLh 
of  a  grain,  but  many  physicians  give  doses  as  large  as  one- thirtieth  of  a 
grain.  The  drug  is  probably  best  taken  in  the  form  of  tablets  (one-sixtieth 
grain)  as  mistakes  are  thus  less  liable  to  occur  regarding  the  size  of  the  dose. 

5.  Wait  fifteen  or  twenty  minutes  (or  longer)  for  the 
drug  to  be  absorbed  and  then  again  test  the  acuteness  of 
hearing,  the  reaction  time  for  sight,  touch  and  sound,  and 
the  acuteness  of  color  sense  with  the  painted  spots  on  the 
tile  (be  sure  these  have  not  changed  their  color  or  appear- 
ance by  drying — the  spots  should  be  thoroughly  dry  be- 
fore the  subject  sees  them  the  iirst  time).  Has  the  strych- 
nine affected  any  of  these  reactions!  Where  did  the  drug 
act  to  do  this?  Is  the  reaction  in  the  nature  of  a  stimula- 
tion or  a  depression?  How  does  this  compare  with  alco- 
hol? 

EXPERIMENT  XXXVII. 

Picrotoxine.     (Frog:     Action  on  Medulla  and  Cord.) 

1.  Examine  the  arrangement  of  the  apparatus  shown 
in  Fig.  208.  Pith  a  frog  {cerehrum  only)  and  arrange  it 
thus  for  recording  contractions  of  the  gastrocnemius  mus- 
cle. Under  the  skin  of  the  back  inject  one  cubic  centi- 
meter of  picrotoxine  solution  (one  cubic  centimeter  equals 


232 


EXPERIMENTAL   PHARMACOLOGY 


I  I  I  I   ^      ^    I  I  1  I  -  n  I 


Fig.    215. — Tracings   from    the    gastrocnemius   muscle   of   a    frog   injected   with   picrotoxine. 

one-half  milligram).  Wait  about  three  to  five  minutes  for 
the  drug  to  be  absorbed,  then  start  the  drum  at  a  moderate 
rate  of  speed.  After  a  short  time  the  frog  will  begin  to 
manifest  certain  symptoms.  Eecord  these  (on  the  lower 
part  of  the  drum^ — the  muscle  contraction  record  should 
have  an  amplitude  of  about  one  and  one-half  or  two  inches) 
and  when  the  first  round  of  the  drum  is  completed  lower 
it  and  wait  a  short  Avhile.  Then  take  a  second  round  of 
contractions  on  the  upper  half  of  the  drum.  How  do  the 
last  contractions  compare  with  the  first  ones  obtained? 
Have  you  studied  any  other  drug  having  a  similar  action  ? 
How  do  you  explain  the  results'? 

Note. — A  method  for  destroying   (cutting  off)   the  cerebrum  while  leav- 
ing the  medulla  intact  is  described  on  page  238. 


ACTIOiSr    OF   PICROTOXINE 


Fig.   216. — Tracings   from   the   gastrocnemius   muscle   of   a   frog  injected   with   brucine. 


EXPERIMENT  XXXVIII. 

Picrotoxine,'''  Chloretone.    (Dog:   Blood-pressure,  Respira- 
tion and  Kidney,  Spleen  or  Intestinal  Loop  Volume.) 

1.  Dissolve  three  grams  of  chloretone  in  about  eight 
cubic  centimeters  of  absolute  alcohol.  Then  add  water 
until  a  slight  precipitate  starts  to  form.  Then  add  a  few 
drops  more  of  alcohol  to  dissolve  the  precipitate.  Now 
observe  carefully  the  method  of  giving  drugs  to  dogs  il- 
lustrated in  Fig.  217.    The  dog  for  this  dose  of  chloretone 

*Picrotoxine   is    not    often    used   in   medicine. 


234  EXPERIMENTAL   PHAEMACOLOGY 

should  weigh  about  eight  or  ten  kilograms.  Some  dogs 
are  considerably  more  susceptible  to  the  drug  than  others. 
One  student  holds  the  animal  between  his  knees  and 
reaches  forward  to  grasp  the  dog  around  the  nose  and 
mouth  with  both  hands  firmly.  The  assistant  slips  a  gag 
(Fig.  218)  into  the  dog's  mouth  just  behind  the  eye  teeth. 


Fig.    217. — Method   of  administering  medicine   to   a  dog  by   means   of   a   stomach   tube. 

The  mouth  is  now  held  closed  and  this  prevents  the  dog 
from  biting  or  dropping  out  the  gag.  A  second  assistant 
should  hold  the  dog's  feet  to  keep  it  from  scratching. 
Sometimes  the  hind  feet  must  be  held  also.  An  ordinary 
soft  rubber  stomach  tube  (or  one-fourth  inch  rubber  tube 
with  a  pointed  end)   is  now  passed  through  the  hole  in 


PRELIMINARY    OPERATlOXh^  -!^)5 

the  gag  and  back  into  the  dog's  mouth.  Pusli  tlie  tube 
into  the  pharynx  and  wait  a  little.  The  animal  will  make 
swallowdng  movement  and  these  help  to  direct  the  tube 
into  the  esophagus.  When  the  tube  is  safely  started  it 
can  be  readil^^  pushed  down  into  the  stomach. 

Caution. — It  not  infrequently  happens  that  the  tube  passes  througli  the 
larynx  and  into  the  trachea.  If  the  drug  be  injected  into  the  lungs  the  animal 
will  die  in  a  few  moments.  This  accident  must  be  carefully  avoided  by  using 
great  caution  in  getting  the  tube  started  far  back  in  the  dog's  mouth.  Also 
when  the  drug  is  given  pour  a  little  of  the  solution  into  the  funnel  and  wait 
to  see  what  results  this  has.  Breathing  sounds  may  sometimes  be  heard  by 
listening  at  the  end  of  the  inserted  tube  if  it  is  in  the  lungs  but  these  are  un- 
trustworthy as  similar  sounds  are  often  heard  when  the  tube  is  in  the  stomach. 


Pii  in.  Hole 


Rubber  tubing 

Fig.    218. — Mouth    gag    for    dogs,    cats    or    rabbits.      Made    of    wood. 

Allow  about  ten  or  fifteen  minutes  for  the  drug  to  act. 
If  the  stomach  was  filled  with  food  the  result  will  not  be 
the  same  as  if  the  stomach  was  empty.  The  animal  often 
becomes  very  lively  and  playful  at  first,  but  soon  gets  weak 
and  unsteady,  especially  in  the  hind  limbs.  After  a  time 
it  lies  down  and  becomes  drowsy  or  even  unconscious.  If 
the  dose  was  too  small  give  a  second  small  amount  after 
fifteen  minutes.  If  the  first  dose  was  large  enough  {and 
too  marked  depression  sliotdd  he  carefully  avoided)  then 
give  a  little  ether  to  bring  on  complete  anesthesia  and  ar- 
range the  animal  for  blood-pressure,  respiratory  and  on- 
cometer (kidney,  spleen  or  intestinal  loop)  tracings.  Iso- 
late both  vagi  and  place  loose  ligatures  around  them.  It 
may  be  necessary  to  give  small  amounts  of  ether  to  keep 
the  anesthesia  sufficiently  deep  at  least  in  the  beginning 


236  EXPERIMENTAL   PHARMACOLOGY 

of  the  experiment.  The  injecting  burettes  contain  adrena- 
lin and  picrotoxine  (one  cubic  centimeter  equals  one-half 
milligram). 

When  the  operations  are  completed  adjust  the  writing- 
points  on  the  drum  and  take  a  normal  record.  Stimulate 
each  vagus  nerve  and  get  records.  How  does  this  affect 
the  respiration  and  circulation?  Now  inject  one  cubic 
centimeter  of  picrotoxine  and  get  records  of  the  results. 
Note  the  time  of  day.  Inject  more  picrotoxine  from  time 
to  time  in  small  doses  (one-half  or  one  cubic  centimeter) 
and  keep  a  close  watch  on  the  heart  action  as  shown  by 
the  amplitude  of  the  manometer  tracing  and  by  the  rate 
of  heart  beat.  There  should  be  a  slowing  of  the  heart 
and  a  fall  of  pressure.  Both  of  these  should  be  brought 
on  very  slowly  and  cautiously  by  small  repeated  doses. 
(Too  large  a  dose  of  chloretone  weakens  the  heart  con- 
siderably and  must  be  watched  in  this  experiment.  It  also 
depresses  the  medulla  somewhat.)  The  heart  beat  should 
become  slow  enough  after  a  time  to  give  a  pressure  trac- 
ing with  an  amplitude  of  about  ten  or  twelve  millimeters 
(one-half  inch)  to  each  stroke  of  the  manometer  pointer. 
When  this  stage  is  reached  lift  up  both  vagi  and  tie  the 
ligatures  tightly.  Does  this  affect  the  heart?  If  not  quickly 
cut  both  vagi  centrally  to  the  ligatures.  Does  this  affect 
the  blood-pressure?  Does  the  respiration  remain  normal? 
How  do  you  account  for  any  changes  observed?  Did  you 
get  satisfactory  records  of  all  these  changes?  If  not  why 
did  you  fail?    Can  you  do  better  next  time? 

Now  stimulate  the  central  end  of  one  vagus  nerve.  How 
does  this  affect  the  animal?  What  nervous  paths  are  con- 
cerned in  this?  Stimulate  the  peripheral  end  of  the  nerve 
and  note  the  effect. 

Inject  more  picrotoxine.  How  does  the  action  here  com- 
pare with  that  in  the  frog?  Inject  some  adrenaline.  Do 
you  get  normal  effects  from  this  dose?      Is    the    heart 


ISOLATIOX   OF   THE    SCIATIC   XERVE 


oo- 

Z.Jl 


slowed?  How  is  the  respiration  affected?  Now  give  sev- 
eral doses  of  picrotoxine  to  kill  the  animal.  What  is  tlie 
immediate  cause  of  death  so  far  as  you  can  judge  by  this 
experiment  ? 


Fig.    219.-— A   dissection    showing   the    position   in    which    an    incision   should   be    made    for 
finding   the    sciatic    nerve    and    placing   a    ligature    around    it    for   stimulation. 

If  time  permits  dissect  out  both  sciatic  nerves  from  the 
outer  and  posterior  aspect  of  each  hind  limb  (see  Fig.  219). 
Ligate  these  nerves  loosely  and  examine  them  carefully  as 


238 


EXPERIMENTAL   PHARMACOLOGY 


to  size,  relations,  and  the  best  .way  to  dissect  them  out 
quickly.  It  is  sometimes  of  much  help  to  dissect  out  one 
of  these  nerves  and  stimulate  it  to  start  up  the  respiration 
in  an  animal  that  has  stopped  breathing  but  in  which  the 
blood-pressure  remains  fairly  high. 

EXPERIMENT  XXXIX. 

Hydrastine.     (Frog:    Spinal  Cord.) 

1.  With  a  pair  of  scissors  cut  off  the  front,  part  of  the 
liead  of  a  frog  (including  the  cerebrum)  as  shown  in  Fig. 
220.  Arrange  the  animal  for  recording  muscular  contrac- 
tions as  shown  in  Fig.  208. 


Cut  on  dotted  line,  just  anterior  to  optic  lobes 


rr.H 


Fig.    220. — Method    for    destroying    (removing)    the   cerebrum   but   leaving   the    rest    of   the 
brain  intact  in   a   frog.      Note  the   position   of  the  section. 

Under  the  skin  of  the  back  inject  one  cubic  centimeter 
of  hydrastine  (sulphate  or  h3^drochloride)  solution  (one 
cubic  centimeter  equals  two  milligrams).  Wait  two  or 
three  minutes  for  absorption  to  occur  and  then  start  the 
drum  at  a  fairly  rapid  speed.  After  a  little  while  there 
should  be  a  marked  reaction.  Try  to  record  the  first  action 
manifested  by  the  frog.  Finish  the  first  round  on  the  drum, 
then  lower  the  drum  and  take  a  second  round.  How  do  the 
reactions  shown  on  the  last  round  compare  with  those  in 


ACTION    OF    IFYDRASTINE 


239 


240 


EXPERIMEI^TAL   PHARMACOLOGY 


the  first  round.  How  do  you  explain  these  effects!  Cut 
the  sciatic  nerve  to  the  muscle  you  are  using.  Is  the  action 
of  the  drug  central  or  peripheral?  Stimulate  the  muscle 
itself  directly  a  few  times  with  single  shocks.  What  does 
this  show? 


Left  Ant  Cav^l  vein 


.night  Ant  Caval  vein 


Pregancjlionic  TTeurCn 

Postqancjiionic  neuron 


Hook  from 
'Heart  lever 


vonBezold's  Ganglion  

/«/Ke/,aca.a/  Ijn  Auricular  septa.      /^.^^^^.     ^^^^^.^^ 

'  In  suriculo-ventricular  junction 


stimulating  electrodes 

in  3ino-auricular  junction  [Crescent] 

Sympathetic  fibres^  dotted  lines 

Fig.  222. — Diagram  to  show  the  innervation  of  the  heart  in  the  frog  or  turtle. 


EXPERIMENT  XL. 


Hydrastine.    (Frog:  Heart  and  Vagus  Nerve.) 

1.  Pith  a  frog  and  dissect  out  the  vagus  nerve  (Fig. 
60).  Arrange  to  record  heart  tracings  and  take  one  inch 
of  normal  record.  Stimulate  the  vagus  nerve  and  get  a 
normal  inhibition.  Then  pour  on  the  heart  a  few  drops 
of  hydrastine  sulphate  solution  (one  cubic  centimeter 
equals  five  milligrams).  How  does  this  affect  the  beat? 
Stimulate  the  vagus  nerve  again  and  record  the  result. 


HYDRASTINE  AISTD  CAFFEINE  241 

What  do  you  observe?  How  do  yon  account  for  this? 
Drop  on  some  more  of  the  drug  and  again  stimulate  the 
nerve.  Is  there  any  change?  Now  take  up  the  electrodes 
and  (Avliile  the  drum  is  going)  turn  on  a  strong  (tetaniz- 
ing)  current.  With  the  extreme  tips  of  the  electrodes  just 
touch  for  a  moment  the  tissues  at  the  base  of  the  heart 
just  where  the  sinus  venosus  joins  the  right  auricle. 
This  is  about  the  point  where  the  inferior  vena  cava  pass- 
ing forward  would  bend  up  toward  the  right  auricle.  The 
inferior  (caudal)  border  of  the  tissue  which  forms  the 
connecting  tube  between  the  sinus  -venosus  and  the  right 
auricle  is  called  the  crescent.  AVhat  result  do  you  ob- 
serve following  a  brief  stimulation  of  this  area?  (Examine 
Fig.  222.) 

EXPERIMENT  XLI. 
Hydrastine.    (Turtle:  Heart  and  Vagus  Nerve.) 

1.  Pith  a  turtle  (brain  and  cord)  and  take  a  normal 
heart  tracing  showing  vagus  inhibition  in  two  or  three 
places.  Lower  the  drum  and  start  a  second  round  of  the 
tracing.  Drop  some  hydrastine  solution  (one  cubic  centi- 
meter equals  five  milligrams)  on  the  heart.  Eecord  the  re- 
sults and  then  stimulate  the  vagus  nerve  again.  What  do 
you  observe?  Apply  more  drug  and  stimulate  again.  Now 
stimulate  the  crescent  and  note  the  results.  What  do  you 
observe?     Can  you  explain  this? 

EXPERIMENT  XLII. 
Caffeine.     (Frog:     Central  Nervous  System,  Muscles.) 

1.  Cut  off  the  front  part  of  the  head  of  a  frog  (Fig. 
220)  and  inject  two  cubic  centimeters  of  caffeine  solution 
(the  free  drug,  not  a  salt,  is  preferable — use  a  saturated 
solution  in  warm  water)  into  the  anterior  lymph  sac  (Fig. 


242 


EXPERIMENTAL   PHARMACOLOGY 


ACTION  OF  CArFElNE  243 

66).  Place  the  frog  in  a  battery  jar  and  examine  it  from 
minute  to  minute.  Do  you  note  any  immediate  symptoms! 
Touch  the  muscles  of  the  hind  legs  from  time  to  time  and 
note  any  changes.  Does  the  animal  have  convulsions?  If 
so,  of  what  character  are  they?  Keep  the  animal  under 
observation  until  it  dies,  watching  the  muscles  carefully. 
Do  you  observe  any  changes  in  these?  If  so,  what  explana- 
tion can  you  offer? 

EXPERIMENT  XLIII. 

Caffeine.     (Frog":    Muscle  and  Nerve.) 

1.  Pith  a  frog  and  isolate  both  gastrocnemius  muscles 
and  both  sciatic  nerves  (attached  to  the  muscles,  i.e.,  nerve 
muscle  preparations).  Determine  the  normal  minimal 
stimulation  to  cause  contraction  in  nerve  A  and  muscle  B. 
Pour  a  small  amount  of  caffeine  solution  into  each  of 
two  watch  glasses.  Into  watch  glass  A  place  the  nerve 
of  one  of  the  muscle  nerve  preparations  and  into  watch 
glass  B  place  the  muscle  of  the  second  preparation. 
From  moment  to  moment  stimulate  the  nerve  of  iDrejDara- 
tion  A  and  the  muscle  of  preparation  B  with  single  shocks. 
What  action  has  caffeine  on  the  vitality  of  nerve  trunks 
and  of  muscle  ?  Which  is  affected  first  ?  Watch  the  mus- 
cle closely  and  note  any  gross  changes  in  appearance,  color, 
length,  solidity,  etc.  What  do  you  observe?  What  ex- 
planation can  you  offer?  Tease  out  some  small  fibers  from 
muscle  A  and  place  them  on  a  slide  and  examine  with  a 
compound  microscope.  Can  you  see  the  cross  striations 
well?  Cover  the  fibers  with  a  cover  glass  and  while  watch- 
ing the  fibrils  closel}^  run  a  few  drops  of  caffeine  solution 
under  the  edge  of  the  cover  glass  in  such  a  manner  that 
the  solution  reaches  the  fibrils  you  are  watching.  What 
effect  has  this  on  the  muscle  fibers?  How  are  the  cross 
and  longitudinal  markings  affected?  How  do  you  ex- 
plain this? 


o 


244  p:xperimei^tal  pharmacology 

EXPERIMENT  XLIV. 
Caffeine.    (Frog:    Heart  and  Vagus  Nerve.) 

1.  Take  a  normal  heart  tracing  from  a  pithed  fro 
(showing  vagus  and  crescent  inhibition).  Drop  caffeine 
(saturated  solution)  on  the  heart  and  record  the  effects. 
Stimulate  the  vagus  nerve  and  note  the  action  of  the  drug 
on  the  inhibitory  nervous  mechanisms.  Apply  more  drug 
and  again  stimulate.  Stimulate  the  crescent  also  and  see 
if  it  is  affected.  Take  several  rounds  of  the  tracing  on  the 
drum  to  get  a  good  insight  into  the  action  of  the  drug  on 
the  heart  muscle.  How  does  this  compare  with  the  action 
on  the  mammalian  heart? 

EXPERIMENT  XLV. 

Caffeine.     (Turtle:    Heart  and  Vagus  Nerve.) 

1.  Repeat  the  previous  exj^eriment  on  a  pithed  turtle. 
Can  you  see  any  changes  in  the  tone  of  the  heart  muscle 
as  indicated  in  your  records? 

EXPERIMENT  XL VI. 
Caffeine.     (Man:    Reaction  Time.) 

1.  As  in  Experiment  XXXVI  (and  XIII)  determine  the 
normal  reaction  time  of  a  student.  Then  allow  the  stu- 
dent to  drink  one  or  two  cups  of  strong  tea  or  coffee  (or 
take  three  grains  of  caffeine  powder  in  capsules)  and  at 
intervals  of  one-half,  one  hour  and  one  and  one-half  hours 
later  again  take  the  student's  reaction  time.  What  do 
you  observe  ?  How  do  you  explain  your  results  ?  On  what 
parts  of  the  central  nervous  system  has  the  caffeine  acted  to 
produce  the  results  observed? 


ACTION  OF   CAFFEliS^E 


245 


EXPERIMENT  XLVII. 
Caffeine.    (Frog:    Muscular  Work.) 

1.  Pitli  a  frog  and  ligate  the  riglit  thigh  tightly  so  as 
to  shut  off  the  circulation.     Fasten  the  animal  down  on  a 


Very  fine  copper 
wires,  aif ached  to 
tack  and  to  tendo 
Achillis 


Fig-.  224. — Arrangement  of  a  frog  and  apparatus  for  recording  "fatigue  tracings" 
from  the  gastrocnemius  muscle.  The  drum  should  have  a  slow  speed.  (For  descrip- 
tion see  text.) 

board  as  shown  in  Fig.  224.  Isolate  the  tendo  Achillis 
of  the  right  leg  and  arrange  as  illustrated  for  stimulating 
with  single  shocks.  The  primary  current  is  best  inter- 
rupted by  a  metronome  as  illustrated,  but  if  this  is  not 


246 


EXPERIMENTAL   PHARMACOLOGY 


availalble  then  a  student  can  interrupt  the  primary  cur- 
rent with  a  simj)le  key  hy  hand  (once  in  one  or  two  sec- 
onds). The  drum  must  have  a  slow  speed.  The  second- 
ary shocks  are  carried  directly  to  the  muscle  by  very  fine 
copper  wires  one  of  wdiich  is  attached  to  the  carpet  tack 
which  is  driven  through  the  frog's  right  knee  into  the  frog 
board  to  hold  the  upper  end  of  the  gastrocnemius  muscle 
firmly  in  place  when  the  muscle  contracts.  The  other  wire 
is  tied  to  the  tendo  Achillis.  Now  inject  into  the  dorsal 
lymph  sac  one  cubic  centimeter  of  five-tenths  per  cent  caf- 


n 


c: 


''lllllll'^*' 


Hubber  tube 
wire 


Cannula  wfh  points  for  cats  a  rabbits 


Point  for  docjs 


Fig.  225. — A  method  for  making  cannulas  with  separable  points.  One  end  of  the 
"T"  of  a  •  glass  (5/16  inch)  T-tube  is  cut  off  short  and  short  glass  points  are  attached 
by  means  of  a  piece  of  rubber  tubing.  It  is  vastly  easier  to  make  the  small  points  than 
to  blow  a  T-tube  and  to  make  a  cannula  entirely  of  glass.  (The  points  illustrated  are 
larger   than   they   should  be   for   rabbits   and   cats.) 

feine  solution   (Greene)   and  allow  this    to    be    absorbed 
while  the  experiment  is  going  on. 

When  all  adjustments  are  made  start  the  drum  and 
record  a  normal  ''fatigue  curve"  from  the  right  gastroc- 
nemius. (For  a  description  of  fatigue  curves  see  any 
manual  on  experimental  physiology.)  This  curve  should 
be  taken  on  the  low^er  half  of  the  drum. 


CAFFEINE    DICRESIS  247 

AVlien  tlie  muscle  is  exhausted  then  ligate  the  left  thigli 
tightly  and  drive  a  second  carpet  tack  through  the  left 
knee  to  hold  tlie  left  gastrocnemius  firmly.  Isolate  the 
left  tendo  Aehillis.  Disconnect  the  stimulating  wires,  re- 
move the  frog  board  from  the  large  clamp  and  turn  the 
frog  board  around  on  a  perpendicular  axis  so  that  the  frog 
will  be  on  the  side  away  from  the  apparatus.  Also  remove 
the  large  clamp,  turn  it  over  on  a  horizontal  axis  and  re- 
attach it  to  the  stand.  Keplace  the  frog*  board.  The  left  leg 
of  the  frog  will  now  occupy  practically  the  same  position 
that  the  right  leg  formerly  had.  Attach  the  stimulating 
wires  and  connect  the  tendon  to  the  muscle  lever.  The 
load,  magnification,  tension,  etc.,  of  this  muscle  must  be 
the  same  as  that  used  with  the  right  muscle.  About  twenty 
minutes  should  now  have  elapsed  for  absorjition  of  the 
caffeine. 

Start  at  the  beginning  of  the  uj^per  half  of  the  drum 
and  record  a  fatigue  curve  of  this  muscle,  which  will  now 
show  the  effect  which  caffeine  has  on  muscular  work.  The 
rate  of  stimulation  should  not  vary  (once  in  one  or  two 
seconds)  for  each  curve.  How  does  the  normal  fatigue 
curve  compare  with  the  caffeine  curve!  What  conclusions 
can  you  draw! 

EXPERIMENT  XL VIII. 
Caffeine.    (Rabbit:    Diuresis,  Cervical  Nerves,  Depressor.) 

1.  Dissolve  two  grams  of  urethane  in  about  twenty-five 
cubic  centimeters  of  water.  Select  a  full  grown  rabbit 
and  with  a  catheter  used  as  a  stomach  tube  inject  the 
urethane  into  the  rabbit's  stomach.  [Pass  the  tube 
through  the  hole  in  a  wood  gag  (Fig.  218)  held  in  the 
animal's  mouth.]  AVait  about  ten  or  fifteen  minutes  for 
the  di'ug  to  be  absorbed  and  then  give  the  animal  a  little 
ether  to  bring  on  complete  anesthesia.  Use  great  care  in 
this  for  rabbits  die  verij  readUij.     Insert  a  tracheal  can- 


248  EXPEEIMEl^TAL   PHARMACOLOGY 

nula  (one-fourth  inch  diameter)  and  connect  up  the  ether 
bottle  (or  anesthetic  device  shown  in  Fig.  116).  Use  the 
greatest  care  in  giving  the  ether  not  to  kill  the  animal.  In- 
to the  femoral  vein  tie  a  very  small  injecting  cannula  (Fig. 
18)  connected  to  a  burette  containing  caffeine  solution 
(.5%).    Record  the  respiration  on  the  drum. 

Open  the  abdomen  over  the  bladder  and  insert  a  bladder 
cammla  (Fig.  23).  Arrange  the  cannula  to  empty  into  a 
graduated  cylinder  and  when  all  preparations  are  made 
wait  ten  or  twenty  minutes  to  record  the  nonnal  rate  of 
urine  secretion.  Test  this  with  Fehling's  solution.  Then 
cautiously  inject  one-half  cubic  centimeter  of  caffeine  so- 
lution into  the  vein.  Watch  the  effects  of  this  on  the 
respiration  closely.    From  time  to  time  as  the  animal  will 


Sliding^  rubber  tube 


I 


ilWiiW^VllWWUWVmW 


^ ^ 

v\/ashour 

Fig.  227. — An  easily  made  glass  cannula  showing  a  sliding  rubber  tube  which  may 
be  used  to  open  or  close  the  small  opening  blown  in  the  side  of  the  tube  and  used  as 
a   "washout." 

tolerate  it  inject  more  caffeine  in  one-half  cubic  centimeter 
(or  smaller)  doses.  Is  there  any  change  in  the  rate  of 
urine  flow?  Collect  the  urine  for  each  ten  minute  inter- 
val. Test  for  reducing  bodies  again.  Is  sugar  present! 
If  so,  how  do  you  account  for  it! 

If  you  have  time,  consult  Fig.  226  to  learn  the  ar- 
rangement of  the  vagus,  sympathetic  and  depressor  nerves 
in  the  neck  of  the  rabbit,  and  then  carefully  dissect  out 
these  nerves.  Using  a  very  small  arterial  cannula  (Figs. 
225  and  227)  connect  the  right  carotid  artery  to  the  ma- 
nometer and  take  a  blood-pressure  tracing.  Stimulate  the 
depressor  nerve  (peripherally)  and  note  the  effect.  How 
do  you  explain  this  result!    Inject  more  caffeine  and  see  if 


CAFFEINE   AXD   SODIUM    SUI-PHATE  249 

you  can  obtain  any  idea  of  the  action  of  tJie  drug  on  the 
heart  and  circulation.  Kill  the  animal  with  a  large  dose 
of  caffeine.  After  the  animal  is  dead  dissect  out  the  vagus, 
sympathetic  and  depressor  nerves  in  the  other  side  of  the 
neck, 

EXPERIMENT  XLIX. 

Caffeine,  Sodium  Sulphate.     (Dog:     Blood-pressure 
Diuresis,  Respiration,  Sciatic  Nerve.) 

1.  Dissolve  three  or  four  grams  of  chloral  hydrate  in  a 
little  water  and  inject  the  solution  into  the  rectum  of  a 
medium  sized  dog.  See  that  the  solution  does  not  run 
out  again  immediately  after  injection.  In  ten  minutes 
anesthetize  the  animal  fully  with  ether  (or  etherize  the 
animal  at  the  start  and  omit  the  chloral  or  give  it  by  stom- 
ach— it  is  advisable  to  give  the  chloral,  how^ever).  Ar- 
range to  record  blood-pressure,  respiration  and  the  rate  of 
urine  flow.  Place  caffeine  (.5%)  and  adrenaline  in  the  in- 
jecting burettes. 

Open  the  abdomen  and  lift  up  the  bladder.  At  the  pos- 
terior side  of  the  base  of  the  bladder  you  w^ill  find  the 
ureters  entering  the  bladder  from  each  side  (see  Fig.  162). 
Pick  up  the  ureters  and  place  in  each  a  ureteral  cannula 
(Fig.  213)  and  arrange  to  record  the  rate  of  urine  secre- 
tion by  obtaining  a  record  on  the  drum  of  the  drops  fall- 
ing from  the  cannulas.  To  do  this  arrange  two  tambours 
as  shoA\Ti  in  Fig.  228  in  such  a  manner  that  each  drop  of 
urine  falls  on  a  small  metal  disc  attached  with  wax  (colo- 
phonium  or  ceiling  wax)  to  the  writing  point  of  the  first 
tambour.  The  second  connected  tambour  records  these 
drops  on  the  drum. 

Consult  Fig.  219  and  dissect  out  the  sciatic  nerve  in  one 
hind  limb.  While  recording  blood-j^ressure  and  respira- 
tion stimulate  the  nerve  with  a  medium  strength  Faradiz- 
ing  current.    What  do  you  observe  I     Can  vou  think  of  a 


250 


EXPERIMENTAL   PHARMACOLOGY 


condition  in  which  this  procedure  might  be  of  help  in  re- 
viving an  animal  I  Try  this  on  the  next  animal  you  have  in 
which  the  respiration  ceases,  especially  if  the  blood-pres- 
sure remains  fairly  high. 

Adjust  all  writing  points,  allow  the  animal  to  return  to 
normal  (keeping  the  anesthesia  as  regular  as  possible)  and 


Drop: 


Metal  plate 


Fig.   228. — Arrangement   of   two   tambours   to   form   a   drop    recorder. 

wait  ten  or  twenty  minutes  to  record  the  normal  rate  of 
urine  floiv.  When  this  is  obtained  (not  a  drop  of  urine 
may  have  been  secreted  during  this  jDeriod,  in  which  case 
simply  watch  for  the  flow  to  start  up)  then  proceed  to  give 
the  caffeine.  AVatch  for  the  effect  on  respiration  and  the 
circulation.  Inject  one  cubic  centimeter  of  caffeine..  What 
do  3^ou  observe?     Increase   the  dose  if  the   animal  will 


ACTION  OF   SODIUM  SULPHATE 


251 


>'H. 


252  .   EXPERIMENTAL   PHARMACOLOGY 

stand  it  and  continue  giving  the  drug  until  several  centi- 
meters are  injected.  Wait  a  while  to  observe  the  effect 
on  urine  flow.  This  often  fails  in  dogs.  Why?  Will  tlie 
chloral  influence  the  result  in  any  Avay? 

Wait  for  fifteen  or  twenty  minutes  for  the  caffeine  to 
act.  Be  sure  the  dose  given  was  large  enough.  Then  al- 
low the  animal  to  become  as  nearly  normal  as  possible  and 
get  a  new  normal  rate  of  urine  flow.  Test  the  urine  for 
sugar.     What  do  you  observe?     Explain. 

Now  empty  the  caffeine  out  of  the  burette  and  fill  it  with 
four  per  cent  sodium  sulphate  solution.  Inject  one  cubic 
centimeter.  Increase  the  dose  rapidly  (twenty  cubic  cen- 
timeters or  more  may  be  given  at  a  time  often  without 
killing  the  animal)  and  Avatch  the  effect  on  blood-pres- 
sure, respiration  and  urine  flow.  What  do  you  observe? 
How  does  this  compare  with  the  action  of  caffeine?  If 
the  animal  is  still  in  fair  condition  substitute  a  four  per 
cent  solution  of  sodium  phosphate  (or  nitrate  or  chloride) 
for  the  sodium  sulphate  and  inject  a  considerable  quantity 
of  this  salt.  How  is  the  rate  of  urine  flow  affected  ?  What 
theories  of  urine  secretion  do  you  knoAV?  On  the  basis  of 
these  explain  the  action  of  the  drugs  injected.  Keep  a 
record  of  the  amount  of  solution  injected  in  each  ten  min- 
ute interval  and  see  if  you  can  collect  an  equal  volume  of 
urine  in  a  beaker  in  the  same  time.  This  can  sometimes 
be  done,  especially  with  rabbits.  Kill  the  animal  by  a 
large  injection  of  one  of  the  salts  mentioned  (watching  the 
urine  flow  as  the  drug  is  acting),  then  dissect  out  the  pan- 
creas and  see  if  you  can  find  its  lower  duct  (Figs.  2-1:4  and 
245).  Could  you  put  a  cannula  in  the  duct  while  the  ani- 
mal was  alive?  Dissect  out  the  gall  bladder,  the  cystic 
duct,  and  the  common  duct.  What  are  the  relations  of  the 
pancreatic  ducts  and  the  bile  ducts  as  the^^  pass  through  the 
wall  of  the  intestine? 


DIURETINE   AISTD  AGUKTXE  253 

EXPERIMENT  L. 

Diuretine,    (Sodium-theobromine-salicylate),  Agurine, 
(Sodium-theobromine-acetate).     (Rabbit:  Diuresis 
and  Respiration.) 

1.  Give  by  stomach  two  grams  of  urethane  dissolved  in 
twenty-five  cubic  centimeters  of  water  to  a  good  sized  rab- 
bit. Wait  ten  minutes  for  the  drug  to  be  absorbed  and 
then  give  the  animal  a  little  ether  to  complete  the  anes- 
thesia. Arrange  to  record  (or  collect  or  both)  the  drojDS 
of  urine  as  they  fall  from  a  bladder  cannula  (or  from  two 
ureteral  cannulas).  Place  a  cannula  in  the  femoral  (or 
jugular)  vein  and  connect  up  a  burette.  Fill  this  with 
diuretine  one  per  cent  (or  agurine,  one  per  cent).  Arrange 
to  record  the  respiration.    Count  the  pulse  rate  per  minute. 

When  all  preparations  are  made  wait  ten  or  twenty  min- 
utes to  obtain  the  normal  rate  of  urine  flow.  Then  inject 
one-half  cubic  centimeter  of  diuretine  [(Ivnoll  and  Com- 
pany, 45  John  St.,  New  York)  or  agurine]  and  record  the 
effect  on  the  respiration.  Count  the  pulse  rate  and  see  if 
it  is  affected.  Now  give  more  of  the  drug  from  time  to 
time  and  try  to  bring  on  the  effect  gradually,  Avatching 
carefully  not  to  kill  the  animal  by  an  overdose.  What  do 
you  observe  1  How  do  you  account  for  this?  If  your  drop 
recorder  does  not  work  well  then  let  a  student  operate 
the  recording  signal  magnet  by  means  of  a  simple  hand 
key  placed  in  series  with  a  dry  cell  and  the  signal  magnet. 
The  student  can  make  and  break  the  current  each  time  a 
drop  falls.  If  you  are  slvillful  enough  you  can  make  a  de- 
vice to  record  each  drop  by  electrical  contact.  But  do  not 
spend  too  much  time  at  this. 

When  you  have  obtained  as  marked  results  as  possible 
from  the  diuretine  (or  agurine  or  both)  then  if  the  rabbit 
is  still  in  suitable  condition  fill  the  burette  with  one  of  the 
following  solutions: 


254  EXPERIMENTAL   PHARMACOLOGY 

2%  sodium  nitrate, 

2%  sodium  i3liospliate, 

2%  sodium  chloride, 

2%  ammonium  chloride, 

2%  ammonium  acetate. 
Arrange  to  observe  the  full  action  on  urine  secretion  and 
cautiously  inject  one-half  cubic  centimeter  (or  less)  of  the 
solution  in  the  burette.  AVitli  great  care  gradually  inject 
more  of  the  solution  from  time  to  time  as  rapidly  as  the 
animal  can  tolerate  it.  What  effect  has  this  on  the  urine 
flow?  Continue  the  administration  as  long  as  satisfactory 
results  can  be  obtained. 


EXPERIMENT  LI. 

Urea,  S.  A.  Matthews'  Solution,  or  Saline  Diuretics. 
(Rabbit  or  Cat:     Diuresis.) 

1.  Repeat  the  above  experiment  with  a  rabbit  or  cat  (us- 
ing two  grams  of  urethane  for  an  average  sized  animal,  or 
1.7  cubic  centimeters  per  kilogram  of  paraldehyde  for  a 
rabbit — Edmunds)  but  after  securing  the  normal  rate  of 
urine  flow  begin  to  inject  one  of  the  following: 

A.  Urea  (5%  solution). 

B.  S.  A.  MaUheiv's  solution: 
NaCl,  3.67  grams. 
Na2S04,  10.1  grams. 
Sodium  Citrate,  3.36  grams. 
CaCl2,  0.136  grams. 
Water,  1000  c.c. 

C.  Three  per  cent  solution  of  any  of  the  following: 
Sodium  sulphate. 

Sodium  phosphate. 
Sodium  nitrate. 
Ammonium  nitrate. 


ACTION    OF    CURARA  255 

Sodium  chloride. 
Sodium  iodide. 

Use  great  care  in  making  the  injections.  Begin  with 
very  small  doses  and  inject  more  as  the  animal  is  able  to 
tolerate  it. 

What  conclusions  can  you  draw  with  reference  to  the 
diuretic  action  of  these  substances?    How  do  they  act! 

EXPERIMENT  LII. 

Curara.     (Frog:     General  Action,  Claud  Bernard's 
Experiment.) 

1.  Pith  a  frog  (cerebrum  onh^)  and  make  a  small  incision 
over  the  back  of  the  right  thigh  (see  Fig.  47).  Dissect  up 
a  short  length  of  the  sciatic  nerve.  Do  not  cut  or  injure  the 
nerve.  Pass  a  thread  beneath  the  nerve  and  tie  off  the  tis- 
sues of  the  thigh  tightly  so  as  to  completely  stop  all  circula- 
tion in  the  right  (gastrocnemius)  muscle  and  foot.  AVith 
single  shocks  stimulate  the  exposed  nerve  once  or  twice  to 
see  hoAV  the  muscles  act  in  the  isolated  part  of  the  leg.  Also 
stimulate  the  tissues  at  the  back  of  the  head  over  the  upper 
end  of  the  cord  once  or  twice  to  get  the  normal  reactions. 
Put  a  drop  of  acetic  acid  on  the  left  hind  foot  and  see  if  the 
animal  moves  the  liml).  Brush  off  the  acid.  Count  the  rate 
of  l3anph  heart  beats. 

Into  the  ventral  l3mipli  sac  inject  one  cubic  centimeter  of 
a  saturated  solution  of  curara.  Wait  three  minutes  and 
then  begin  to  retest  the  reflexes  from  time  to  time  as  the 
drug  is  absorbed.  How  is  the  rate  of  beat  of  the  lymph 
hearts  affected?  Will  the  animal  jump  when  stimulated? 
As  the  action  of  the  drug  becomes  very  marked  stimulate 
again  the  exposed  sciatic  nerve.  (Keep  the  nerve  moist  "\AT.th 
salt  solution  where  it  is  exposed.)  Apply  a  drop  of  acetic 
acid  to  the  skin  of  the  back.  Is  there  any  response  ?  If  so, 
Avhere  ?    Stimulate  the  upper  end  of  the  cord.    What  muscles 


256 


EXPEKIMENTAL   PHARMACOLOGY 


respond!  Stimulate  the  left  gastrocnemius  (through  the 
skin)  directly.  Does  it  contract?  What  conclusions  can 
you  draw?  Where  does  curara  act?  Does  your  experiment 
prove  the  nerve  trunks  are  not  paralyzed  ?  Are  the  sensory 
nerve  endings  paralyzed?  Does  your  experiment  give  you  a 
chance  to  test  this  point?     Count  the  l3anph  heart  rate 


Fig.  230. — Tracing  showing  the  action  of  a  solution  of  curara  dropped  on  the  heart 
of  a  frog.  Lower  line  normal,  showing  the  inhibition  caused  by  stimulation  of  the 
vagus  trunk.  Second  line,  curara  was  applied  at  "x"  and  the  vagus  was  again  stimulated 
as  shown  by  the  short  line  and  legend.  Third  line,  the  application  of  the  drug  was  con- 
tinued and  the  vagus  trunk  was  again  stimulated  as  indicated.  No  noticeable  results  fol- 
low the  stimulation.  Why  not?  Fourth  and  fifth  lines,  application  of  the  drug  was  con- 
tinued and  its  action  on  the  heart  is  shown. 

again.  What  conclusions  can  you  draw  from  this  ?  What 
is  the  action  of  curara  on  the  central  nervous  system?  (See 
McGuigan:  Journal  of  Pharmacology  and  Experimental 
Therapeutics,  1916,  viii,  p.  471.) 

Do  you  knoAv  of  any  other  substances  possessing  an  ac- 
tion on  motor  nerve  endings  in  striated  muscles  like  curara 
does  ?  How  does  this  drug  differ  from  atropine  in  its  action 
on  nerve  endings? 


Cenfer  for  ^  ,^^,  --,^,/.. 
cranial  secretprKf/b^^w 


Facial  nerv^iiN.VII 
Cerebellum,  ^ 
Giossophdrynqeal/^nerve^ 

Medulla  oblongata 
Parotid  gland 


Cord- 


.^/v,.    Center  for  --I'l) 
"////^^)/asodilator  ner'^'s 

'''f.yf^^/M///'/opi\c  ganglion 

^ner^i^^P^^""'""^'"  ^'^^^^^^'^^ )  ganglion 
(n  \/)^^^^°''^^  '^y'^P^^'  nerve 
i^/V.  V  l^m^i^fjjgii  superficial  '" 

petrosal  nerve 
Pon^^>J^'^^lnf  max.  div.  N.  V 

Q^'xr'  Jacobson's 


\^ 


nerve 


tympani 
branches/ 


Parotid  duct 
(5ten  son's) 

Submaxillary 
duct  {Wharton's} 

■Sublingual 
duct 

{Bartholin's) 
Lingual  nerve 
Chordo-lingual 

triangle 


t. 


Electrodes 
( Large  amount  of  thin 
saliva, 
vasodilatation 

^Sublingual  gland 


'^Superior 
cervical  gang. 

'Submaxillary 
Electrodes^  aland 

^{5mall  amount  of  thick  saliva 
vaso- constriction  ) 

Waso  constrictor  fibers 
sympathetic  secretory  fibers 

^Outgoing  sympathetic 
rami  communicantes 

Post-  ganglionic  fibers  are 
dotted  thus  — 

Fig.     231. — Diagrammatic    representation     nf    the    innervation    of    the    salivary    glands    m 

the"  dog. 


ACTION    OF    CURARA  257 

EXPEKIMENT  LIII. 
Curara.    (Frog:    Heart  and  Vago-sympathetic  Nerve.) 

1.  Pith  a  frog  and  arrange  to  take  a  heart  tracing. 
Stimulate  the  vagus  nerve  and  get  a  normal  inhibition. 
Drop  on  the  heart  a  few  drops  of  a  saturated  curara  solu- 
tion. What  do  you  observe?  Now  stimulate  the  nerve 
again  and  record  the  result.  Has  any  change  been  pro- 
duced! If  not  apply  more  curara  and  stimulate  again. 
Now  stimulate  the  crescent  and  record  the  result.  A^Tiat 
do  you  observe?  How  do  you  explain  this?  Apply  more  of 
the  drug  to  bring  out  the  later  action  on  the  heart. 

EXPERIMENT  LIV. 
Curara.    (Turtle:    Heart  and  Vagus  Nerve.) 

1.  Repeat  the  above  experiment  on  a  pithed  turtle. 
How  do  the  results  obtained  with  this  animal  conijoare  with 
those  from  the  frog?  "What  is  the  innervation  of  the  tur- 
tle's heart?    How  does  it  differ  from  that  of  the  frog? 

EXPERIMENT  LV. 

Curara,  Strychnine.     (Dog  or  Cat:    Blood-pressure,  Respi- 
ration, Urine,  Sciatic  Nerve.    Dog:  Salivary 
Ducts  and  Nerves.) 

1.  Weigh  a  medium-sized  dog  and  give  it  by  stomach 
three  hundred  milligrams  of  chloretone  per  kilo  of  body 
weight.  Dissolve  the  chloretone  in  ten  cubic  centimeters  of 
alcohol  (absolute)  and  dilute  the  solution  as  much  as  pos- 
sible with  water.  Add  a  little  alcohol  to  redissolve  any  pre- 
cipitate formed.  After  ten  minutes  etherize  the  animal  and 
attach  it  to  the  operating  l^oard.  Arrange  to  record  blood- 
pressure  and  respiration  (stethograph).    The  injecting  bu- 


258  EXPEKIMENTAL   PHARMACOLOGY 

rettes  contain  strychnine  (one  cubic  centimeter  equals  one- 
lialf  milligram)  and  adrenaline.  (If  a  cat  must  be  used  give 
it  two  grams  of  urethane  in  twenty-five  cubic  centimeters 
of  water  by  stomach,  or  give  1.7  cubic  centimeters  of  paral- 
dehyde per  kilogram  of  animal — Edmunds.) 

Insert  a  bladder  cannula  into  the  fundus  of  the  dog's 
bladder,  draw  off  a  little  urine  and  test  it  with  Fehling's 
solution.  Do  you  get  a  reduction!  If  so  how  do  you  explain 
it  ?  Now  consult  Fig.  219  and  dissect  out  the  sciatic  nerve 
using  great  care  not  to  disturh  the  vessels  of  the  leg.  (These 
are  carefully  avoided  so  the  curara  can  be  well  distributed 
to  the  muscles  innervated  by  the  sciatic.)  Stimulate  the 
sciatic  with  a  medium  strength  Faradizing  current  and 
note  the  effect  on  resjDiration  and  blood-pressure  and  on  the 
muscles  of  the  leg  below  the  point  of  stimulation. 

Beneath  the  skin  of  the  back  or  side  inject  mth  a  hypo- 
dermic syringe  twenty  cubic  centimeters  of  a  saturated  solu- 
tion of  curara  (Merck's).  This  dose  is  exceedingly  large  if 
the  drug  is  pure,  but  it  is  usually  impossible  to  get  a  first- 
class  preparation  of  the  substance  in  this  country.  Note 
the  time  of  day  and  observe  how  long  a  time  is  required  for 
the  drug  to  act  (slow  or  weaken  or  stop  the  respiration). 
How  is  the  blood-pressure  affected?  (It  may  be  necessary 
to  give  more  of  the  drug  later.)  Be  on  the  watch  for  the 
respiration  to  become  shallow.  How  does  this  aifect  the 
blood-pressure!  Be  sure  to  keep  the  anesthesia  going  if 
the  dose  of  chloretone  was  not  sufficient  to  completely  main- 
tain the  narcosis.  This  drug  is  supposed  not  to  prevent 
sensation,  hence  the  animal  must  be  kept  anesthetized.  As 
the  respiration  begins  to  fail  give  artificial  respiration. 
This  must  be  maintained  during  the  remainder  of  the  ex- 
periment. 

From  time  to  time  briefly  stimulate  the  vagus  nerve  with 
a  medium  tetanizing  current  and  note  the  effect  on  the 
heart.  Do  you  observe  any  change  after  the  action  of  the 
drug  has  become  very  marked!     Is  there  any  change  in 


ACTION"    OF    CURAKA  259 

the  reaction  of  the  pupil  when  the  vago-sympathetic  trunk 
is  stimulated? 

Collect  a  few  drops  of  urine  and  test  with  Fehling's  solu- 
tion.   Is  there  any  reduction?    How  do  you  account  for  it? 

Pick  up  the  sciatic  and  stimulate  it  again  with  the  same 
strength  of  current  as  that  used  the  first  time.  Do  you  get 
a  response?  What  conclusions  can  you  draw?  How  does 
electrical  stimulation  compare  mth  the  natural  nervous  im- 
pulse ? 

NoAv  get  the  animal  in  as  good  condition  as  possible  and 
while  recording  the  blood-pressure  inject  one  cubic  centi- 
meter of  strychnine.  Follow  this  up  rapidly  mth  more 
injections  as  fast  as  the  animal  can  well  tolerate  the  drug. 
Watch  for  con\'Tilsions.  Do  you  get  these?  What  muscles 
are  atfected  by  curara?  What  ones  are  not  affected?  Does 
the  action  of  strychnine  extend  to  any  of  those  not  affected 
by  curara?  If  so  Avhat  manifestations  of  this  action  would 
you  expect?  Are  these  present?  Is  there  any  change  in 
blood-pressure?  If  so  how  long  is  this  change  present  as 
compared  mth  the  action  of  strychnine  in  a  noncurarized 
animal?  Explain  this.  Stimulate  the  vagus  and  sciatic 
uprves  again  and  note  the  results  on  the  heart  and  leg  mus- 
cles. Is  there  any  change  in  blood-pressure  when  the  sciatic 
is  stimulated?  If  so  how  does  this  compare  Avith  your  nor- 
mal record?  What  structures  are  involved  and  how  are 
they  affected  (Bayliss:  Journal  of  Physiology,  Ixxx,  353)? 

Dog.— Consult  Figs.  237,  238,  239  and  240  and  dissect  out 
the  submaxillar}^  and  sublingual  ducts.  Also  dissect  out  the 
chorda  t^mipani  nerve.  For  the  general  distribution  of 
nerves  to  the  salivary  glands  see  Fig.  231.  If  the  ainmal  is 
still  in  suitable  condition  try  to  insert  a  cannula  (Fig.  102) 
into  Wharton's  duct  as  indicated  in  Figs.  238,  239,  and  21:0. 
Stimulate  the  chorda  tympani  nerve  and  see  if  you  can  ob- 
serve any  effects  on  the  rate  of  salivary  secretion.  AMiat 
action  has  curara  on  the  salivary  apparatus?  Have  you 
demonstrated  this?     Kill  the  animal  with  a  large  dose  of 


260  EXPERIMENTAL   PHARMACOLOGY 

strychnine.  After  death  dissect  out  the  ducts  and  chorda 
tympani  nerve  on  the  opposite  side.  Can  you  easily  dif- 
ferentiate between  the  two  ducts?  Can  you  locate  the 
chordo-lingual  triangle?  Cut  out  (label)  both  eyes  and 
place  them  in  thirty  per  cent  alcohol.  Save  for  dissection 
later. 

EXPERIMENT  LVI. 

Coniine.     (Frog^:  Heart  and  Vagus  Nerve.) 

1.  Pith  a  frog,  arrange  for  taking  a  heart  tracing  and 
stimulate  both  the  vagus  trunk  and  the  crescent.  Get  rec- 
ords showing  the  inhibition  from  each  of  these.  Drop  two 
or  three  drops  of  a  one  per  cent  coniine  solution  on  the 
heart.  How  does  this  affect  the  record?  Now  stimulate  the 
vagus  and  crescent  again  and  record  the  results.  "What  do 
you  observe  1  How  do  you  explain  this !  A¥hat  other  struc- 
tures are  similarly  affected  by  coniine  ?  Make  a  diagram  of 
the  innervation  of  the  heart  (Fig.  222)  of  the  frog  in  your 
permanent  note  book  and  indicate  on  it  the  structures  af- 
fected by  coniine  and  state  the  nature  of  this  action.  Apply 
sufficient  coniine  to  the  heart  to  bring  it  to  a  standstill.  Do 
you  know  of  any  other  drugs  that  act  lilve  coniine  ?  "Watch 
for  these  later. 

EXPERIMENT  LVII. 

Coniine.    (Turtle:  Heart  and  Vagus  Nerve,  Lungs  and 
Sympathetic  Nerves.) 

1.  Repeat  Experiment  LVI  on  a  turtle  and  secure  rec- 
ords to  show  the  action  of  the  drug.  After  a  record  show- 
ing the  specific  action  of  the  drug  on  the  ganglia  has  been 
obtained  (how  would  3^ou  prove  this?)  then  unhook  the 
heart  lever  and  remove  the  turtle  from  the  drum.  (It  is 
often  advisable  to  use  a  fresh  turtle  for  this  part  of  the  ex- 
periment.   Large  turtles  are  preferred.)     Consult  Pig,  232 


To  tambour 


Hook 


Leg 

done 

(cun 


Fllunq 

parhally 

inflated 


. bronchus 


Leg 

bone 

(cut) 


Heart 
L  lung 
partially 
inflated 


Position  occupied  by  hind 
limbs  (removed) 


Fig.  232. — A  turtle  with  the  Ijrain  and  spinal  cord  destroyed  and  with  the  plastron 
and  most  of  the  viscera,  limbs  and  skeletal  muscles  removed  to  expose  freely  the  partially 
inflated  lungs._  A  bull-dog  is  placed  on  the  right  bronchus  to  exclude  the  right  lung 
from  communication  with  the  recording  tambour  which  is  connected  with  the  left  lung 
by  means  of  the  glass  cannula  tied  in  the  trachea.  The  electrodes  are  shown  placed 
under  the  left  vagus  trunk.  The  heart  beats  freely.  Stimulation  of  the  vagus  nerve 
causes  a  marked  contraction  of  the  corresponding  lung.  (See  Fig.  233  for  arrangement 
of  the  recording  apparatus.) 


262 


EXPERIMENTAL   PHARMACOLOGY 


and  note  carefully  what  has  been  removed.  Cut  the  plas- 
tron loose  at  each  side  and  remove  it.  Lift  up  the  intestines 
and  liver  and  with  great  care  dissect  them  loose  from  the 
lungs.  To  do  this  put  a  cannula  (Fig.  233)  into  the  trachea 
and  attach  a  rubber  tube.  Then  mth  the  mouth  blow  the 
lungs  up  as  indicated  in  the  illustration  and  clamp  off  the 
rubber  tube.    This  holds  the  lungs  partially  distended  and 


.--■    /y^/'<*<-i 


Fig.  233. — Arrangement  of  apparatus  with  a  turtle  held  in  a  Higgin's  turtle  frame 
(of  3/8  inch  iron  rod  with  hooks  at  the  corners  to  which  the  limbs  are  tied)  for  record- 
ing lung  contractions.  A  very  sensitive  large-bowled  tambour  with  a  large  magnification 
is  used,  and  the  lungs  are  partially  inflated  by  forcing  a  little  air  (with  the  mouth)  into 
the  side  outlet  of  the  tubing.  This  puts  the  tambour  and  the  lung  both  under  moderate 
tension  and  in  direct  communication.  When  the  lung  contracts  the  tambour  pointer 
rises  but  when  the  lung  relaxes  the  pointer  descends  as  the  rubber  membrane  on  the 
tambour  forces  the  air  back  into  the  lung.  Drugs  are  conveniently  administered  by  in- 
jection into   the   heart   with  a   fine  pointed   hypodermic   syringe. 

greatly  aids  in  the  dissection.  Use  great  care  not  to  punc- 
ture the  lungs.  If  you  do  this,  find  the  hole,  lift  up  the 
edges  of  the  opening  and  tie  a  ligature  around  the  puncture. 


TURTLE  LUNC  TEACIjNT'G 


263 


When  the  entrails  are  removed  \  len  cut  out  all  tlie  skeletal 
muscles  you  can  including  the  entire  hind  limbs  and  most  of 
the  muscles  of  the  fore  limhs.  This  exposes  the  lungs  prac- 
tically free  from  skeletal  muscles. 

Connect  the  tracheal  cannula  with  a  tambour  (very  sensi- 
tive, medium-sized  bowl)  and  bring  the  writing  point  on  to 
a  slow  drum.    Observe  the  way  the  bull-dog  is  placed  in  the 


^tuyy^. 


Fig.    234. — Tracing    showing    the    contraction    of    the   left    lung    of   a    turtle    when    the   left 
vagus   nerve   was   stimulated   electrically. 

figure.  In  a  similar  manner  clamp  off  one  bronchus  and 
then  pick  up  the  main  trunks  of  the  vagus  and  s>anpathetic 
nerves  on  the  opposite  side  well  up  in  the  neck.  See  that 
the  lung  is  partially  inflated  and  the  tambour  under  a  slight 
tension.  Start  the  drum,  and  with  a  fairly  strong  tetaniz- 
ing  current  stimulate  the  vagus  and  sympathetic  trunks 


264 


EXPERIMENT/ -L   PHARMACOLOGY 


(see  Fig.  234).  What  do  you  observe?  What  are  your  con- 
clusions? Consult  your  text-book  on  physiology  for  further 
explanation  regarding  the  innervation  of  the  lungs.     Now 


^  fi'htJiXU%,'tJUU)Jtl^ 


iKiiimiiiiiiiinniiiiiiimiiiissiiiiiiiiiimiiimiiiimiiiri 


Fig.  235. — Lung  and  heart  tracings  from  a  turtle  showing  the  effect  of  electrical 
stimulation  of  the  right  vagus  nerve  (first  contraction  and  inhibition)  and  of  mechanical 
stimulation    (tearing)    of    the   same   nerve    (second    and   third   records). 

make  a  careful  dissection  of  the  nerves  (and  sympathetic 
branches)  on  the  opposite  side  of  the  neck.  Make  a  sketch 
of  these  nerves  for  future  reference. 

It  is  exceedingly  desirable  in  making  the  preliminary  dis- 
section to  remove  as  much  as  possible  of  the  skeletal  mus- 
culature. This  prevents  movements  which  may  be  confused 
with  the  lung  contractions. 


ACTION    OF    CONIINE 


265 


Fig.    236. — Diagrammatic    representation    of   the    innervation    of   the   lachrymal    glands. 


EXPERIMENT  LVIII. 

Coniine.      (Dog:     Blood-pressure,    Respiration,    Salivary- 
Glands  and  Kidney,  Spleen  or  Intestinal  Loop.) 

1.  In  the  usual  manner  j)repare  a  dog  (ten  or  twelve 
kilos)  for  recording  blood-pressure  and  respiration.  The 
animal  may  be  given  morphine,  twenty  milligrams  (one 
cubic  centimeter  of  two  per  cent  solution)  per  kilogram  of 
body  weight  half  an  hour  before  the  operation,  or  ether 
alone  may  be  used.    The  injecting  burettes  contain  coniine 


266 


EXPERIMEl^TAL   PHARMACOLOGY 


(one  per  cent)  and  adrenaline.  (Poor  samples  of  coniine 
are  frequently  obtained.)  Isolate  and  ligate  loosely  .both 
vago-syinpathetic  nerves. 

Consult  Figs.  237,  238,  239,  and  240,  and  dissect  out  Whar- 
ton's duct.  Place  a  cannula  {very  small)  in  the  duct  and 
fasten  it  with  a  ligature  (thread).  Dissect  out  the  chorda 
tympani  nerve  and  when  you  can  see  it  clearl}^  lying  across 
the  tip  of  the  sublingual  gland  then  place  the  ends  of  the 


Fig.  237. — A  dissection  showing  the  position  and  extent  of  the  first  incision  for  ex- 
posing the  chorda  tympani  nerve  and  the  ducts  from  the  submaxillary  and  sublingual 
glands. 

electrodes  on  the  nerve  and  stimulate  it.  Do  you  get  a  nor- 
mal result?  If  not  why  did  you  fail!  (Dissect  out  the  op- 
posite duct  and  nerve  if  necessary.)  Consult  Fig.  231  for 
the  general  distribution  of  nerves  to  the  gland.  Are  any 
other  glands  thus  innervated?    If  so  what  ones? 

Open  the  abdomen  and  place  an  oncometer  on  a  kidney 
(left),  spleen  or  an  intestinal  loop.  Close  the  abdomen  with 
hemostats  and  arrange  all  writing  points  in  the  following 


Angle  of  jaw 
Trachea 


Fig.  238. — Dissection  showing  the  position  and  relation  of  the  hypoglossal  and 
lingual  nerves  (dotted  and  colored  yellow)  beneath  the  thin,  band-like  mylohyoid  muscle 
which  is  to  be  torn  across  with  a  blunt  probe  (tiot  with  a  scalpel)  to  expose  the  nerves 
(and  ducts)   beneath. 


Torn  edqe  of 
mylohyoid  muscle 


Diqaslric 
muscle 


Vein," 
in  fascid 


Sublingual  duct 
( Bartholin's) 

Submaxillary  duct 
(Whartons) 

Lingual  nerve 


Mylohyoid  muscle 
displaced  mesially 

Hypoglossal  nerve 


Fig.    239. — The    mylohyoid    fibers   have    been   torn   across   and    the    two   ducts   and   the 
lingual   and    hypoglossal    nerves   are    exposed. 


Fig.    240. — Exposure    of   the    chorda   tympani    nerve,   Wharton's    duct    and    Bartholin's    duct. 
Method  of  procedure  for  inserting  a  cannula  into   Wharton's  duct. 


I 


ACTION   OF   CONIINE  267 

order  from  above  do^ai,  oncometer,  blood-pressure,  respira- 
tion, base  line  and  time  signal.  Take  a  normal  record,  in- 
cluding a  vagus  stimulation,  and  then  inject  one  cubic  centi- 
meter of  coniine  solution.  Watch  the  pupils  as  the  drug  is 
injected.  Do  you  obtain  satisfactory^  results?  How  did  the 
heart  beats  appear  just  after  the  drug  was  injected?  How 
do  you  account  for  this  ?  Stimulate  the  vagus  nerve  again 
and  record  the  result.  Has  any  more  saliva  been  secreted  ? 
How  do  you  account  for  any  changes  in  the  oncometer  trac- 
ing. Inject  a  small  dose  of  adrenaline  to  see  if  your  appa- 
ratus, etc.,  is  working  satisfactorily. 

Inject  a  second  dose  of  coniine.  This  may  be  larger  or 
smaller  than  the  first  dose  depending  on  the  reactions 
brought  about  by  previous  injections.  Do  you  get  a  fall  in 
blood-pressure?  If  so  how  do  you  explain  it?  If  you  get  a 
rise  what  is  the  cause  of  this?  Stimulate  the  vagus  again 
and  explain  its  action  on  the  heart.  Observe  the  corre- 
sponding pupil  while  the  nerve  is  stimulated.  Stimulate  the 
chorda  and  see  if  any  change  has  been  produced  in  it  as 
shown  by  the  salivary  secretion.  Explain  any  changes  ob- 
served. From  time  to  time  give  more  coniine  as  the  animal 
Avill  tolerate  it.  Be  ready  to  apply  artificial  respiration  if 
necessary.  At  intervals  stimulate  the  vagi  and  chorda  and 
if  a  response  fails  to  be  obtained  explain  its  cause.  Then 
follow  the  course  of  the  chorda  tympani  back  under  the  jaw 
bone  as  far  as  you  can  (do  not  injure  the  duct)  and  finally 
push  the  electrodes  far  down  into  the  hilus  of  the  gland  and 
stimulate.  Can  you  cause  any  visible  increase  in  the  flow  of 
saliva  by  this  procedure?  What  is  the  purpose  of  tliis  part 
of  the  experiment?  Give  some  adrenaline  and  see  if  the 
pupils  respond  normally. 

Open  the  abdomen,  follow  the  right  side  of  the  stomach 
around  posteriorly  and  pick  up  the  duodenum.  In  the 
angle  between  this  and  the  stomach  (inferiorih^)  is  located 
the  pancreas.  Refer  to  Figs.  244  and  245  and  find  the  lower 
end  (tail)  of  the  pancreas.    Follow  this  to  the  place  Avhere 


268  EXPERIMENTAL   PHARMACOLOGY 

its  attachment  to  the  duodenum  begins.  The  large  duct 
(Fig.  245)  opens  into  the  intestine  about  one-half  inch 
above  this  attachment.  To  find  the  duct  take  a  probe  and 
with  great  care  gently  dissect  the  anterior  edge  of  the  pan- 
creas away  from  the  wall  of  the  intestine.  The  duct  will  be 
found  passing  from  the  substance  of  the  pancreas  obliquely 
downward  and  inward  through  the  intestinal  wall.  Pass  a 
ligature  beneath  the  duct  as  shown  in  Fig.  245  and  then 
open  the  duct  in  the  substance  of  the  bowel  wall.  Insert  a 
small  cannula  and  tie  it  in  with  the  ligature.  Attach  a  short 
rubber  tube  to  the  cannula  and  bring  it  outside  the  abdomen 
which  is  now  closed  with  hemostats. 

Give  another  dose  of  coniine  and  see  if  you  get  any  secre- 
tion from  the  pancreas.  Stimulate  the  vagi  nerves  and  note 
any  effect  on  pancreatic  secretion.  Kill  the  animal  with  a 
big  dose  of  coniine.  Immediately  after  death  quickly  open 
the  thorax,  pick  up  the  phrenic  nerves  and  stimulate  them 
with  a  weak  tetanizing  current.  Does  the  diaphragm  con- 
tract I  What  theories  do  you  know  concerning  the  cause  of 
death  under  coniine  (Cushny:  Journal  of  Experimental 
Medicine,  i,  202)  ?  Dissect  out  the  small  duct  of  the  pan- 
creas. What  is  the  innervation  of  the  pancreas?  How  is 
its  secretion  controlled! 

EXPERIMENT  LIX. 
Atropine.     (Frog:   Heart  and  Vagus  Nerve.) 

1.  Pith  a  frog  and  take  a  normal  heart  tracing  showing 
the  effects  of  stimulating  the  vago-sympathetic  nerve  and 
the  crescent.  Then  while  the  drum  is  going  pour  two  drops 
of  atropine  sulphate  solution  (one  cubic  centimeter  equals 
one  milligram)  on  the  heart.  After  a  few  seconds  stimulate 
the  vagus  trunk  again.  What  do  you  observe  f  How  do  you 
explain  it  1  Now  stimulate  the  crescent.  What  do  you  ob- 
serve ?    How  do  you  explain  this  f 

2.  Cut  out  both  of  the  frog's  eyes.     Examine  the  size 


ACTION   OF   ATROPINE  269 

of  the  pupils  carefully.  Place  one  eye  in  a  watch  glass  full 
of  normal  salt  solution  and  the  other  in  atropine  solution. 
Place  both  glasses  aside  for  ten  or  twenty  minutes.  Then 
again  compare  the  size  of  the  pupils.  Do  you  note  any  va- 
riations?   Explain  the  results. 

EXPERIMENT  LX. 

Atropine.     (Frog:   Muscle  and  Nerve.) 

1.  From  the  frog  used  in  Experiment  LIX  prepare  two 
muscle  nerve  preparations  from  the  sciatic  nerves  and  gas- 
trocnemius muscles.  Fill  a  watch  glass  with  atropine 
solution  and  place  the  nerve  of  preparation  A  and  the 
muscle  of  preparation  B  in  the  solution.  From  time  to  time 
stimulate  both  nerves  with  single  shocks  and  determine 
whether  or  not  atropine  affects  either  nerve  trunks  or  stri- 
ated muscle.  Compare  this  with  the  action  of  curara. 
Stimulate  the  muscles  directly  a  few  times.  What  con- 
clusions can  you  draw? 

EXPERIMENT  LXI. 

Atropine.    (Turtle:   Heart  and  Vagus  Nerve.) 

1.  Repeat  the  experiment  on  the  heart  and  vagus  inner- 
vation described  in  Experiment  LIX,  1,  on  the  turtle.  What 
conclusions  can  you  draw  from  your  results  ? 

EXPERIMENT  LXII. 

Atropine.     (Cat,  Guinea  Pig,  Rat,  Dog,  Pigeon,  or 
Chicken:    Pupil.) 

1.  Secure  a  dog,  guinea  pig  or  rat  and  a  iDigeon  or 
chicken.  Into  the  right  eye  of  each  animal  pour  several 
drops  of  a  one  per  cent  solution  of  atropine  with  a  medicine 
dropper.    Place  the  animals  aside  and  examine  from  time 


270  EXPEKIMENTAL   PHAKMACOLOGY 

to  time  to  see  if  any  changes  are  produced  in  the  eyes.  If 
so  what  explanation  can  you  offer.  If  no  change  is  pro- 
duced what  explanation  can  you  give  ? 

EXPERIMENT  LXIII.* 

Atropine.     (Dog,  Cat  or  Rabbit:   Blood-pressure,  Respira- 
tion, Heart  and  Vag^us  Nerve, — Dog,  Salivary  Secre- 
tion and  Chorda  Tympani,  Sweat  Nerves, 
Pancreatic  Secretion.) 

1.  Anesthetize  a  dog,  cat  (two  grams  urethane  by  stom- 
ach) or  rabbit  (two  grams  urethane  by  stomach)  and  ar- 
range for  recording  blood-pressure  and  respiration.  Iso- 
late and  ligate  loosely  both  vagus  nerves.  The  injecting 
burettes  contain  atropine  (one  cubic  centimeter  equals  one- 
half  milligram)  and  adrenaline  (1:10,000). 

If  a  dog  is  used  dissect  out  Wharton's  duct  and  place  a 
cannula  in  it  (Figs.  237,  238,  239,  and  240).  Also  isolate 
the  chorda  tyiupani  nerve  and  stimulate  it  once  or  twice  to 
observe  the  normal  rate  of  salivary  secretion.  Some  opera- 
tors tie  a  ligature  on  the  chorda  and  cut  the  nerve  centrally 
to  the  ligature.  In  this  manner  the  ligature  can  be  used  to 
lift  the  nerve  as  desired.  Generally  it  will  be  sufficient 
to  stimulate  the  nerve  in  position  without  ligating  it.  (The 
dissection  may  be  tried  on  a  cat  or  rabbit  if  the  instructor 
so  advises.) 

Stimulate  the  vagi  and  obtain  normal  records  of  the  ef- 
fects on  the  heart,  blood-pressure  and  respiration.  Observe 
the  pupils  (on  the  same  side)  as  each  vagus  nerve  is 
stimulated. 

If  time  permits,  the  student  may  dissect  out  the  sciatic 
nerve  (in  dog)  and  stimulate  it  to  observe  the  secretion  of 
sweat  on  the  sole  of  the  foot.  To  do  this  take  a  piece  of 
wet  cotton  and  wash  the  pads  of  the  foot  off  well,  then  dry 


*If   more  than   one   group    performs   this   experiment,   the   second   group   may   use   scopo- 
lamine— one  cubic  centimeter  equals  one  milligram — instead   of  atropine. 


ACTIOiSr   OF  ATROPINE  271 

them  and  place  the  foot  in  such  a  manner  that  a  good  light 
can  fall  at  a  slight  angle  on  to  the  pads.  A  hand  lens  may 
be  used  to  considerable  advantage.  Stimulate  the  corre- 
sponding sciatic  nerve  and  watch  for  minute  droplets  of 
sweat  to  form  on  the  pads.  On  that  side  of  the  animal  it  is 
advisable  not  to  place  a  cannula  in  the  femoral  vein  but  in- 
sert the  cannula  in  the  external  jugular  vein  instead.  Do 
not  injure  the  circulation  in  isolating  the  sciatic  nerve. 

Arrange  all  writing  points  on  the  drum  (medium  speed) 
and  Avhile  taking  a  normal  (satisfactory)  record  begin  to 
stimulate  one  vagus  nerve  mth  a  weak  or  medium  strength 
of  current  (tetanizing).  The  current  should  be  of  just  great 
enough  strength  to  slow  the  heart  markedly  but  not  to  com- 
pletely stop  it.  Do  not  continue  this  any  longer  than  neces- 
sary or  the  vagus  endings  may  be  worn  out.  While  thus 
holding  the  heart  do^\m  to  a  slow  rate  by  a  constant  stimula- 
tion (increase  the  strength  of  the  current  if  necessary)  of 
the  nerve  inject  two  cubic  centimeters  of  atropine  solution 
(for  a  dog, — if  a  cat  or  rabbit  is  used  inject  one-half  or  one 
cubic  centimeter  of  atropine  solution). 

Continue  the  stimulation.  Do  3^ou  observe  any  change 
after  the  drug  has  had  time  to  be  carried  to  the  heart  in 
the  blood?  (Remember  the  circulation  is  slow  and  sluggish 
when  the  heart  beats  but  slowly  and  the  pressure  is  low). 
How  do  you  explain  your  findings?  Now  inject  another 
dose  of  atropine  as  soon  as  the  animal  can  tolerate  it.  Then 
stimulate  the  opposite  vagus  nerve  and  note  the  effect  on 
the  heart  rate  and  blood-pressure.  Stimulate  the  chorda 
tympani  and  note  the  effect  on  salivary  secretion.  How  do 
you  explain  this? 

Examine  the  sole  of  the  foot  (dog)  carefully  for  sweat 
droplets  (remove  these  if  any  are  present)  and  then  stimu- 
late the  sciatic  again.  What  conclusions  can  you  draw? 
Were  you  able  to  get  a  sweat  secretion  by  stimulation  of  the 
sciatic  before  the  drug  was  injected?  If  not  what  does  this 
part  of  the  experiment  show?    Again  stimulate  one  vagus 


272  EXPERIMENTAL   PHARMACOLOGY 

and  watch  the  effect  on  the  (corresponding)  pupil.  What 
changes,  if  any,  do  yon  note?    How  do  yon  explain  these! 

What  effect  has  atropine  in  small  doses  on  the  blood- 
pressnre  and  respiration!  A  poisonous  drug  suddenly  in- 
jected into  the  circulation  often  gives  a  fall  of  pressure  due, 
according  to  some  authorities,  to  irritation  of  the  heart. 
Do  you  believe  this  explanation  is  sufficient  to  account  for 
such  changes!  The  vasomotor  centers  and  the  vessels,  etc., 
may  also  be  specifically  involved.  ^Hiat  action  has  atropine 
on  the  vasomotor  apparatus! 

If  the  experiment  is  performed  on  a  cat  or  rabbit  kill  the 
animal  with  a  large  dose  of  the  drug  and  secure  a  death 
record.  If  a  dog  is  used  inject  a  little  adrenaline  and  ob- 
serve the  action  of  this  on  the  pupil  (explain).  Open  the 
abdomen  and  insert  a  cannula  (Figs.  244  and  245)  into  the 
pancreatic  duct.  Inject  twenty  cubic  centimeters  of  .4% 
hydrochloric  acid  into  the  duodenum  with  a  large  hypo- 
dermic syringe  and  wait  ten  or  twenty  minutes  to  see  if 
there  is  any  secretion  of  pancreatic  juice.  How  is  the  secre- 
tion of  the  pancreas  controlled !  What  action  has  atropine 
on  this  mechanism!  What  effect  will  stimulation  of  the 
vagus  nerves  now  have  on  the  pancreas!  Try  this  (use 
slowly  repeated  single  shocks).  Inject  some  adrenaline  and 
see  if  this  affects  the  secretion. 

Kill  the  animal  with  a  large  dose  of  atropine,  securing  a 
death  record  of  the  blood-pressure  and  respiration.  What 
is  the  immediate  cause  of  death! 

2.  If  time  permits  after  the  animal  is  dead,  consult  Fig. 
281  and  dissect  out  the  optic  nerve  at  the  posterior  side  of 
the  eye  ball.  Be  careful  not  to  injure  the  blood  vessels. 
With  scissors  cut  the  skin  and  fascia  outwards  (backwards) 
from  the  outer  canthus  of  the  eye.  Then  seize  the  fascia 
over  the  back  of  the  eye  ball  with  forceps  and  roll  the  ball 
forward  (inward).  A  mass  of  orbital  fat  and  fascia  will  be 
seen  behind  the  eye.  Carefully  dissect  this  away  and  watch 
for  the  optic  nerve  which  is  about  three  millimeters  in  di- 


SCOPOLAMINE,   PILOCARPHsTE,  ATP.OPINE  Zi  6 

ameter  as  it  enters  the  eye  ball.  Place  the  tips  of  the  elec- 
trodes on  the  nerve  and  carefully  work  the  points  into  the 
substance  of  the  nerve  trunk.  Watch  the  pupil  closely  and 
stimulate.  Is  there  any  action?  Perhaps  the  animal  has 
been  dead  too  long.  Do  you  think  of  any  other  reason? 
Master  the  technic  of  the  operation  for  you  will  want  to 
repeat  it  later.  What  is  the  innervation  of  the  iris? 
How  do  these  nerves  get  into  the  eye?  Can  you  reach  them 
in  the  way  you  have  proceeded  here?  What  are  mydri- 
atics ?    Myotics  ?    Cycloplegiacs  ? 

EXPERIMENT  LXIY. 

Scopolamine.    (Frog:  General  Symptoms.) 

1.  Into  the  anterior  lymph  sac  of  a  frog  inject  one 
cubic  centimeter  of  scopolamine  (one  cubic  centimeter 
equals  five  milligrams).  Put  the  animal  in  a  quiet  place 
and  observe  the  symptoms  produced.  What  conclusions 
can  you  draw*?  Examine  the  pupils  from  time  to  time  and 
note  the  action  on  the  lymph  heart  beats.  Give  a  larger 
dose  if  necessary  to  bring  on  marked  s>anptoms. 

EXPERIMENT  LXV. 

Pilocarpine,  Atropine.   (Frog:  Heart  and  Vagus  Nerve.) 

1.  Pith  a  frog,  take  a  normal  heart  tracing  showing 
vagus  and  crescent  inhibition  and  then  while  the  drum  is 
running  at  a  fairly  slow  speed  begin  to  drop  on  to  the  heart 
pilocarpine  (nitrate  or  hydrochlorate)  solution  (one  cubic 
centimeter  equals  one  milligram).  Watch  for  a  slowing 
of  the  beat.  The  heart  may  be  entirely  stopped.  How  do 
you  account  for  this?  When  the  slowing  has  become  very 
marked  pour  about  three  or  four  drops  of  atropine  solu- 
tion (one  cubic  centimeter  equals  one  milligram)  on  to  the 


274 


EXPEKIMENTAL   PHAEMACOLOGY 


heart  and  note  the  effect  on  the  heart  rate.    How  do  you 
explain  this!    Stimulate  the  vagus  and  crescent  again. 

2.  Cut  out  both  eyes  and  place  one  in  a  normal  salt  solu- 
tion, the  other  in  salt  solution  containing  pilocarpine  (one 
cubic  centimeter  equals  five  milligrams).  Place  the  eyes 
aside  for  ten  or  twenty  minutes  and  examine  the  pupils 
again.  Can  you  detect  any  pupillary  changes?  What  ex- 
planation can  you  offer? 


Fig.   241. — Lung  tracing  from  a  turtle  showing  the  action  of  pilocarpine. 


EXPERIMENT  LXVI. 

Pilocarpine  or  Arecoline  and  Atropine. 

Circulation.) 


(Frog:     Retinal 


1.  Arrange  a  frog  as  shown  in  Fig.  164  and  examine  its 
retinal  blood  vessels  with  an  ophthalmoscope.  Find  one  or 
two  very  small  vessels,  preferably  showing  a  branching  so 
that  the  individual  corpuscles  can  be  seen  moving  into  each 
di\dsion.  Get  a  good  notion  of  the  rate  of  this  movement 
for  later  comparison. 

Under  the  skin  of  the  back  inject  two  cubic  centimeters 
of  pilocarpine  solution  (one  cubic  centimeter  equals  two 
milligrams)  or  arecoline  hydrobromide  (one  cubic  centi- 
meter equals  one    milligram,    Merck    and    Co.)    solution. 


Descending^ 
\sympathetic  fibres 
in  spinal  cord 


tmaxi 

Cervical  sympathetic 


Fig.   242. — Schematic   representation  of  the   general   plan   of  distribution  of   the   nerves 

from    the    medullary    centers    to    the    salivary    glands.      This    distribution    is  typical    for    a 

considerable    number    of    other    structures,    glands,    muscles,    etc.,    located  in    the    head. 
(Partially  adopted   from   Eycleshymcr  and   Schoemaker.) 


Fig.  243. — Dissection  of  the  submaxillary  and  sublingual  glands  and  their  ducts,  certain 
cranial  nerves  and  arteries  and  of  the  cervical  sympathetic  trunk  and  the  superior  cervical 
ganglion.     (^Modified  from  Claud  Bernard.) 


PILOCARPINE,   ARECOLINE,   ATROPINE  275 

From  moment  to  moment  observe  the  eye  ground  and 
watch  for  any  change  in  the  rate  of  capillary  movement. 
If  you  succeed  well  in  getting  a  change,  then  with  a  tine 
pointed  hypodermic  syringe  inject  into  the  pericardium 
one-half  cubic  centimeter  of  atropine  solution  (one  cubic 
centimeter  equals  one  milligram).  What  changes  do  you 
observe  in  the  retinal  circulation?  How^  do  you  explain 
this? 

EXPERIMENT  LXVII. 

Pilocarpine  or  Arecoline  and  Atropine.    (Dog,  Cat,  Rabbit, 
and  Pigeon  or  Chicken:    Pupil.) 

1.  Into  the  right  eye  of  as  many  of  these  animals  as 
may  be  available  inject  about  twenty  droios  of  pilocarpine 
(one  cubic  centimeter  equals  live  milligrams)  or  arecoline 
(one  cubic  centimeter  equals  three  milligrams)  solution. 
Open  the  lids  and  fill  the  conjunctional  sac  as  completely 
as  possible  and  keep  the  solution  in  as  long  as  you  can. 
Into  the  left  eye  of  each  animal  drop  atropine  solution  (one 
cubic  centimeter  equals  four  milligrams).  Leave  the  ani- 
mals alone  quietly  and  at  intervals  of  a  few  minutes  com- 
pare the  two  eyes.  Do  you  note  any  pupillary  changes? 
Explain  these. 

EXPERIMENT  LXVIII. 

Pilocarpine,  Atropine.    (Dog:  Blood-pressure,  Respiration, 
Salivary  and  Pancreatic  Secretions.) 

1.  Anesthetize  a  ten  kilo  dog  (ether  only)  and  arrange 
to  record  blood-pressure  and  respiration.  Insert  a  cannula 
in  Wharton's  duct  (Figs.  237,  238,  239  and  240)  and  dis- 
sect out  the  chorda  tympani.  Stimulate  it  and  get  a  nor- 
mal secretion. 

Open  the  abdomen  and  insert  a  cannula  into  the  large 


276  EXPERIMENTAL  PHARMACOLOGY 

pancreatic  duct  (Figs.  244  and  245).  Stimulate  the  vagus 
nerve  Avith  a  series  of  single  shocks  repeated  at  frequent 
intervals  (does  this  stop  the  heart?)  and  see  if  you  can  get 
a  flow  of  pancreatic  juice.  Keep  this  up  for  five  or  ten 
minuses  if  necessary. 

Thr  ^e  injecting  burettes  should  be  used,  one  in  each 
iemor. i,  vein  and  one  in  the  left  external  jugular  vein. 


Fig.  244.-y-A  dissection  showing  the  position  and  relations  o£  the  pancreatic  ducts 
in  a  dog.  I,  intestine;  O,  omentum;  M,  mesentery;  S,  stomach;  P,  pancreas  (tail);  BD, 
position  of  bile  duct  (dotted,  beneath  the  pancreas)  ;  LD,  large  duct,  and  SD,  small  duct 
of  the  pancreas.     The  pancreas  is  partly  cut  away  to  show  the  position  of  the  ducts. 

This  latter  one  contains  adrenaline,  the  other  two  contain 
atropine  (one  cubic  centimeter  equals  one  milligram)  and 
pilocarpine  (one  cubic  centimeter  equals  one  milligram). 
Observe  the  size  of  the  pupils  carefully.  Then  adjust  all 
writing  points  and  take  a  short  normal  record.  Inject  one 
cubic  centimeter  of  pilocarpine  solution.    "What  is  the  ac- 


ACTION  OF  PILOCAKPINE  AND  ATROPINE  277 

tion  of  this  drug  on  the  heart  and  circulation?  Is  there 
any  action  on  the  glands?  Be  sure  no  atropine  gets  into 
the  vein  until  you  are  entirely  ready  for  it. 

When  the  animal  recovers  inject  more  pilocarpine.  Be 
sure  you  get  in  enough  to  bring  out  the  action  of  the  drug 
well.  The  animal  is  not  likely  to  die  early  if  srnal  doses 
are  used.  Note  the  action  on  the  pupils,  salivary  glands 
and  pancreas.  How  do  you  explain  this?  Inject  one-half 
cubic  centimeter  of  adrenaline  and  see  how  this  counter- 
acts the  action  of  the  pilocarpine.  Examine  the  pads  of  the 
feet  and  see  if  any  small  sweat  drops  are  forming.  (Re- 
member the  circulatory  disturbance  you  have  caused  in  the 
hind  limbs.)  Inject  more  pilocarpine  and  try  to  get  as 
marked  action  on  the  heart  as  possible.  In  a  good  typical 
case  a  long  series  of  carotid  tracings  may  be  obtained  in 
which  separate  heart  beats  may  have  an  amplitude  of  from 
one-half  up  to  three-fourths  of  an  inch.  When  this  stage 
is  reached  quickly  observe  the  rate  of  salivary  and  pan- 
creatic secretion  and  then  inject  one  cubic  centimeter  of 
atropine.  This  will  not  reach  the  heart  for  some  time. 
Wait  and  see  what  happens.  Explain  all  results  observed. 
On  what  structures  does  each  drug  act?  If  necessary  in- 
ject one  cubic  centimeter  more  of  atropine.  Now  inject 
one-half  cubic  centimeter  of  adrenaline  to  restore  the  ani- 
mal. Stimulate  the  chorda  tympani  and  the  vagi.  What 
effect  has  this  on  the  salivary  or  pancreatic  secretion? 
How  does  the  vagus  stimulation  affect  the  heart,  blood- 
pressure,  and  respiration? 

Observe  carefully  your  record  of  respiration  just  after 
the  pilocarpine  was  first  injected.  Is  there  a  peculiar  de- 
crease in  amplitude  with  some  difficulty  in  either  expira- 
tion or  inspiration?  What  possible  explanation  can  you 
offer  for  this?    How  did  the  atropine  affect  it? 

Inject  one  cubic  centimeter  more  of  pilocarpine.  Is  the 
heart  slowed?  On  what  structures  does  atropine  antago- 
nize the  action  of  pilocarpine  ?    What  is  the  action  of  pilo- 


278  EXPEKIMEJSTTAL   PHARMACOLOGY 

carpine  on  the  adrenal  glands?  (Dale  and  Laidlaw:  Jour- 
nal of  Physiology,  1912.) 

Kill  the  animal  with  a  large  dose  of  pilocarpine  and  ob- 
tain a  death  record.  Watch  the  pupils  as  the  drug  is  in- 
jected. What  do  you  observe?  What  is  the  immediate 
cause  of  death? 

If  time  permits  open  the  chest  and  tit  into  it  a  piece  of 
apparatus  like  that  shown  in  Fig.  255  (or  Fig.  256,  if  you 
happen  to  have  this).  Close  the  chest  with  hemostats  as 
shown  in  Fig.  257.  Could  you  do  this  in  a  living  animal? 
Kemove  and  wash  all  your  apparatus. 

EXPERIMENT  LXIX. 

Pilocarpine,  Arecoline,  Adrenaline,  Atropine,  and  Barium. 
(Dog:  Bladder,  Intestine,  Respiration,  Blood-pressure.) 

1.  Etherize  a  dog  and  arrange  to  record  blood-pressure 
and  respiration.  Open  the  abdomen  and  connect  a  mercury 
bulb  to  the  bladder  in  the  manner  shown  in  Figs.  179  and 
199  and  arrange  to  record  bladder  contractions  on  the 
upper  part  of  the  drum  (the  tambour  pointer  will  rise 
when  the  bladder  contracts — allow  space  for  this.) 

Observe  the  apparatus  shown  in  Fig.  246  for  recording 
intestinal  contractions.  Arrange  a  burette,  catheter  and 
finger  cot  (or  rubber  glove  finger)  as  shown  and  make  a 
small  longitudinal  incision  in  a  loop  of  tlie  small  intestine. 
Slip  the  end  of  the  catheter  over  which  the  finger  cot  is  at- 
tached about  four  or  five  inches  down  the  lumen  of  the  in- 
testine from  the  incision.  (The  tip  of  the  catheter  reaches 
entirely  to  the  end  of  the  finger  cot  and  thus  forces  the  cot 
along.)  Fill  the  burette  half  full  of  water  and  move  the 
catheter  in  and  out  a  little  to  be  sure  the  finger  cot  is  filled 
ivith  water  and  that  the  air  is  expelled.  Stitch  together 
the  incision  in  the  intestine  around  the  catheter  and  close 
abdomen  with  hemostats.     The  intestinal  tambour  should 


Fig.  245. — Dissection  showing  the  position  and  relations  and  the  method  of  isolating  the  large 
duct  of  the  pancreas  in  a  dog.  The  method  for  inserting  a  cannula  into  the  duct  where  it  lies 
within  the  wall   of  the  intestine  is  also  shown. 


RECORDIjN^G   INTESTIlSTAL   COiS^TRACTIONS 


279 


write  just  below  the  bladder  (the  pointers  must  be  able  to 
pass  each  other),  below  this  are  the  blood-pressure,  respi- 
ration and  base  line.    The  injecting  burettes  contain  pilo- 


Fig.    246. — Arrangement   of   apparatus    for    recording   contractions    of    the    intestine.      (For 

discussion   see   text.) 

carpine  (one  cubic  centimeter  equals  one  milligram)   and 
adrenaline. 

Take  two  inches  (or  less)  of  normal  record  and  then  in- 
ject one  cubic  centimeter  of  pilocarpine.  A  pronounced  re- 
sult should  be  obtained  in  all  the  tracings.     Do  you  get 


280 


EXPERIMENTAL   PHARMACOLOGY 


this  ?  Wait  for  the  action  of  the  drug  to  become  well  de- 
veloped. If  you  are  sure  the  dose  was  too  small  then  inject 
a  second  (but  one  cubic  centimeter  is  usually  sufficient  for 


Fig.  247. — Tracing  showing  the  action  of  barium,  adrenaline  and  atropine  on  the 
blood-pressure  and  intestinal  contractions  in  a  dog.  The  barium  had  been  given  just 
before  this  tracing  begins.  Its  action  on  the  inSestine  is  quite  evident  but  the  contrac-_ 
tions  are  checked,  first  by  adrenaline  (which  stimulates  the  inhibitory  endings)  and. 
second  by  atropine.     How  do  you  explain  this  latter  action? 


BARIUM,    ADRENALINE,    PILOCARPINE 


281 


average  sized  dogs).  When  the  effects  are  well  marked 
inject  one-half  cubic  centimeter  of  adrenaline.  What  pilo- 
carpine reactions  does  this  counteract?  Your  records 
should  show  marked  results. 


^ — (2<T>WL.<Let^<rKvi  I 

1.  .(^BscyOxA^)      I 


.^ixm'^'itKf^mKmm 


/-  loOOQ. 


(UVliWljIU^w^^ 


■,4U7^-  O  jSp^txryiAA, 


Fig.   24B. — Tracing   showing  the   comparative   extent   of   duration    of  the   action   of   barium 
and  of  adrenaline  on  intestinal  contractions  and  on  the  blood-pressure  in  a  dog. 

Allow  the  animal  to  return  to  normal  and  then  repeat 
the  pilocarpine  and  adrenaline  injections. 

Allow  the  animal  to  recover  for  a  few  minutes  and  mean- 
while empty  the  pilocarpine  out  of  the  burette  and  replace 


oUt-CttAi^-tAoiXluciA. 


ritJt,AAAAAJL^ 


I 


5^ 


Fig.  249. — Tracing  showing  the  action  of  arecoline  and  of  atropine  on  intrathoracic 
pressure,  bladder  contractions  and  blood-pressure  in  a  dog.  Intrathoracic  pressure  was 
recorded  by  means  of  a  tambour  with  a  moderatel/  tightly  stretched  ruliber  membrane. 
The  tambour  was  connected  with  a  glass  tube  which  was  passed  into  the  chest  cavity 
(without_  letting  air  in'o  the  chest).  Arecoline  strongly  contracts  the  bronchioles  and 
thus  shrinks  the  volume  of  the  lungs.  This  drew  air  out  of  the  tambour  into  the  chest 
and  caused  the  writing  point  to  write  at  a  lower  level.  The  bladder  and  heart  both  show 
a  marked   reaction  to   the   drug.      These  effects  are   partially   counteracted   by   the   atropine. 


Sympathefic    chain 

Pudic  nerve  fibers    ^ 
(Motor.  dl5o  vaso-consfrictor) 

Corpu3  cavernosum 


H^llccf^. 


Pelvic 
ganglia 

Retractor  penis  muscle^ 
'Corpus  spongiosum 
Urett)ra  Pelvic{Erigens)nerve  fibers 

(Inhibitory,  also  vaso-dilator) 
(Erection) 


Fig.    250.— Schematic    representation    of    the    innervation    of    the    retractor    penis    muscle 
Ihe    vasomotor   innervation    for    the    region    is    also    indicated. 


ARECOLINE    AND   ADRENALHSTE 


233 


it  with  arecoline  solution  (one  cubic  centimeter  equals  one- 
lialf  milligram). 

Adjust  all  Avriting  pointers  and  take  a  normal  record. 
Inject  one  cubic  centimeter  of  arecoline.    This  will  give  pro- 


F.g.   251. — Tracing  showing  the  action  of  pilocarpine  on   the   rate   of   oxygen   consumption, 
intestinal  contractions,  blood-pressure  and  respiration. 

found  results.  Wait  for  the  drug  to  act  and  when  the 
symptoms  are  very  marked  inject  adrenaline  (probably 
three-fourths  cubic  centimeter).     Wait  for  the  animal  to 


284 


EXPERIMENTAL   PHARMACOLOGY 


recover  as  much  as  possible.  Give  a  second  dose  of  adren- 
aline if  necessary.  Then  empty  out  the  adrenaline  (be 
sure  the  bull-dog  on  the  vein  does  not  leak)  and  fill  this 
burette  with  twenty  cubic  centimeters  of  atropine  solution 
(one  cubic  centimeter  equals  one  milligram.) 


X  [-<m. 


/OSS  MMx-£% 


Fig.  252. — Tracing  showing  the  action  of  a  fatal  dose  of  barium  chloride  on  uterine  con- 
tractions,   blood-pressure    and    respiration. 

Get  the  animal  into  as  good  condition  as  possible  and 
then  inject  one  cubic  centimeter  (or  one  and  one-half  cubic 
centimeters)  of  arecoline.  Wait  for  the  action  of  the  drug  to 
become  well  developed  and  then  inject  one  cubic  centimeter 
of  atropine.  Wait  for  this  to  be  carried  to  the  heart.  What 


ADRENALINE  AND  BARIUM 


>85 


Fig.   253. — Tracing  showing  the  action  of  adrenaline  and  barium  chloride   (after  atropine) 
on    the    heart     (myocardiogram)     and    blood-pressure. 


286 


EXPERIMENTAL   PHARMACOLOGY 


^.OuaUA, 


™''^lil^ 


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C/^£,>Ax;t(n,yJU 


"I'M 


,'€ift, 


i 


.^.OtAoti^ 


wmmiimMmmiif^^*\ 


mmm 


Fig.  254. — Tracing  showing  the  action  of  a  fatal  dose  of  barium  chloride  on  the 
heart  (myocardiogram,  right  auricle  and  left  ventricle)  and  blood-pressure  in  a  dog. 
Note   that  the   auricle   continues  to   beat   long  after   the   ventricle    has  stopped. 


PILOCARPINE,  ADRENALINE,  ARECOLINE,  ETC.  287 

do  YOU  observe?  How  do  you  account  for  it?  Pilocarpine 
acts  very  much  like  arecoline  (as  does  also  muscarine)  but 
arecoline  is  much  more  powerful. 

Does  atropine  counteract  all  the  actions  of  pilocarpine 
or  arecoline!  Do  your  records  show  this?  Inject  one-half 
cubic  centimeter  more  of  atropine.  Then  empty  the  atro- 
pine out  of  the  burette  and  replace  it  with  barium  chloride 
solution  (one-half  per  cent).  Arrange  all  writing  points 
and  inject  one  cubic  centimeter  of  arecoline  to  see  if  it  acts 
as  it  previously  did.  Empty  out  the  arecoline  and  replace 
it  mth  adrenaline.  If  the  dog  weighs  ten  kilos  or  more 
then  inject  five  cubic  centimeters  of  the  barium  solution  (a 
smaller  dose  for  a  smaller  dog).  It  will  take  about  one- 
half  minute  for  the  action  of  the  drug  to  become  well 
marked  (if  the  animal  was  in  fair  condition  when  the  drug 
was  injected).  The  reaction  should  be  very  marked. 
When  this  occurs  inject  one  and  one-half  cubic  centimeters 
of  adrenaline.  Does  this  counteract  any  of  the  actions  of 
barium?  On  what  structures  does  barium  act?  Did  the 
previous  administration  of  atropine  affect  this  in  any  way  ? 
Kill  the  animal  with  a  big  dose  of  barium  and  just  after 
the  death  record  is  made  quickly  open  the  chest  {with  large 
tinner's  snips)  and  observe  the  heart  action.  What  is  delir- 
ium cordis?    "WTiat  is  fibrillation? 

EXPERIMENT  LXX.* 

Pilocarpine,  Adrenaline,  Arecoline,  Atropine,  Barium. 
(Spinal  Dog:    Blood-pressure  and  Bronchioles.) 

1.  Etherize  a  dog  (ten  kilos)  and  arrange  for  blood- 
pressure  records.  Place  injecting  burettes  in  both  femoral 
veins  and  one  in  the  left  external  jugular.  These  burettes 
contain  adrenaline  (1:10,000),  pilocarpine  (one  cubic  cen- 
timeter equals  one  milligram)    and  arecoline    (one  cubic 

*Cats  may  be  used  for  this  experiment,   but  dogs  are  greatly  to  be  preferred. 


EXPERIMENTAL   PHARMACOLOGY 


centimeter  equals  one-half  milligram).  (Muscarine — one 
cubic  centimeter  equals  one  milligram — may  be  substituted 
for  one  of  the  last  two  drugs  or  be  used  separately  if  it 
is  available.) 

Observe   carefully  the   apparatus   shown   in   Fig.    255. 


Flancie  for 
sawed  edge 
of  sternum 


Biaphraqmattc 

'  surface 

Fig.  255. — A  form  of  apparatus  (approximately  one-half  natural  size)  made  of,  sheet 
brass  to  place  in  the  chest  to  hold  the  walls  rigidly  wide  open  and  air  tight  while  the 
records  of  changes  in  the  caliber  of  the  bronchioles  are  taken.  A  dotted  circle  in  the 
center  of  the  curved  plate  shows  where  a  window  may  be  placed  to  great  advantage  if 
sufficient  shop  facilities  are  available  to  do  this.  The  window  may  be  made  of  a  sheet 
of  celluloid  (such  as  is  used  in  automobile  curtains)  or  of  glass,  and  if  the  window  is 
removable  this  also  adds  to  its  usefulness.  The  curved  wire  at  the  base  is  made  9f  3/16 
inch  brass  rod.  Any  tinner  should  easily  be  able  to  make  up  at  a  very  small  cost  such  a 
piece  of  apparatus,  which  can  be  made  of  "tin"  (tinned  iron)  or  galvanized  sheet  irori. 
The  instrument  may  be  used  for  recording  bronchial  contractions  by  use  of  either  posi- 
tive or  negative  artificial  respiration,  but  the  latter  (aspiration  of  the  chest)  is  greatly 
to  be  preferred.      (For   the   method   of  use  see  text.) 


KECORDING  BRONCHIAL  CHANGES 


289 


This  ai3i)aratns  works  best  when  the  air  is  intermittently 
aspirated  out  of  the  chest  (25  or  30  times  per  minute — 
45  millimeters  of  mercury  negative  pressure  with  the  by- 
pass or  inlet  adjusted  to  give  |)roper  strength  of  suction 
to  fill  the  lungs  well).  In  the  absence  of  a  machine  capable 
of  giving  negative  interrupted  pressure  (see  Fig.  360)  pos- 
itive artificial  respiration  ma^^^  be  used  in  the  ordinary 
manner  by  blowing  air  into  the  trachea.  Even  a  hand  bel- 
lows may  be  used  for  this,  but  a  i^ower  driven  machine  is 


/G/asj  window 

-Removeble  cap 

Tube  for 
aspirafion 


AdjusPeible  ''y-P^'frm^^^^^^Flancje  for  sternum 

Diaphragmatic  -#-!|^^^Bfi  ^^^^^Costal  surface 
SOrface 


tiotdi,for 
peric&rdi&l  sac 
^  inf  vena  cava 

Fig.  256. — Another  form  of  apparatus  for  insertion  into  the  chest  to  record  bronchial 
•changes.  About  one-third  natural  size.  The  three  wings  at  the  bottom  are  placed  inside 
the  chest  and  are  adjustable  (by  the  thumb  nuts)  to  fit  various  sized  chests.  When  the 
cap  (with  a  glass  or  celluloid  window)  is  removed,  the  hand  may  be  passed  into  the 
■chest  to  massage  the  heart,  etc.  The  movements  and  changes  in  the  lungs  and  heart 
can  be   seen  through  the   window.      (For  the  method   of   use  see   text.) 

greatly  to  l)e  i^referred.    The  ajDpaiatus  shown  in  Fig.  256 
may  also  be  used  for  the  lungs. 

The  chest  of  the  animal  is  now  o^Dened  by  a  median  lon- 
gitudinal incision,  the  apparatus  is  inserted  as  sho^m  in 
Fig.  257  and  the  edges  are  clamped  around  air  tiglit  with 
hemostats.  It  is  often  advisable  to  sew  one  or  two  stitches 
of  heavy  twine  from  side  to  side  through  the  skin  of  the 
upper  end  of  the  chest.  The  flange  of  the  apparatus 
catches  the  sawed  eds-es  of  the  sternum  on  each  side  and 


290 


EXPEKIMENTAL   PHARMACOLOGY 


thus  holds  the  chest  open.  As  soon  as  the  chest  is  opened 
artificial  (positive)  respiration  is  begun.  Two  forms  of 
apparatus  for  thus  giving  ether  to  an  animal  are  shown  in 
Figs.  53  and  107.  The  artificial  respiration  thus  begun 
is  kept  up  throughout  the  experiment  if  only  positive  pres- 
sure is  available.  But  if  negative  (interrupted)  pressure 
is  available  this  is  substituted  immediately  after  the  ani- 
mal is  pithed. 
If  positive  pressure  is  used  then  the  closed  chest  acts  as 


'^^/tdju stable  by-pass 


Fig.  257. — Adjustment  of  the  apparatus  shown  in  Fig.  255  in  the  chest  of  a  dog.. 
The  sawed  edge  of  the  sternum  catches  against  the  flange  of  the  apparatus  and  the  skin- 
and  fascia  are  brought  up  and  clamped  tightly  with  hemostats  to  the  edges  of  the  plate. 
One  or  two  stitches  may  be  taken  to  draw  the  chest  together  at  the  front  end  of  the 
Piiparatus.  If  vosi  ive  artificial  resvjiration  is  used  this  aopa'-atus  simply  converts  the 
chest  into  a  rigid-walled  plethysmograph  or  oncometer  for  the  lungs  and  heart.  A  glass- 
(or  celluloid)  window  aids  greatly  by  allowing  the  operator  to  see  when  the  lungs  are 
being  sufficiently   inflated. 

an  oncometer  and  the  tube  to  the  recording  tambour  (which 
should  have  a  large  hoivl)  is  connected  to  the  tube  labeled 
"aspirate"  in  Fig.  255.  Thus  when  the  lungs  are  blomi 
full  of  air  through  the  trachea  and  are  thus  expanded  air 
will  be  forced  out  of  the  chest  and  into  the  tambour  the 
pointer  of  which  will  rise.    Conversely  when  the  lungs  col- 


PRELIMI]!TARY    OPEEATIOj!^S  291 

lapse  air  will  be  drawn  into  the  chest  from  the  tambour 
and  the  pointer  will  descend.  If  the  bronchial  muscles 
contract  or  dilate  the  extent  of  this  movement  will  be  cor- 
respondingly decreased  or  increased.  The  extent  of  ex- 
pansion or  contraction  of  the  lungs  can  be  controlled  by 
the  screw  clamp  on  the  tracheal  cannula  (if  the  volume  of 
air  delivered  by  the  respiration  machine  at  each  inflation 
cannot  be  independently  controlled).  The  extent  of  move- 
ment of  the  tambour  pointer,  i.  e.,  of  the  amount  of  air  en- 
tering or  leaving  the  tambour  bowl,  can  be  controlled  by 
the  screw  clamp  on  the  ''inlet"  of  Fig.  255. 

If  negative  pressure  is  used  this  is  applied  only  after  the 
dog  is  pithed  (this  being  determined  by  the  administration 
of  the  ether  which  is  better  done  by  positive  artificial  respi- 
ration). Figure  257  shows  the  way  to  arrange  the  tubes  to 
the  apparatus.  In  this  case  the  tiihe  to  the  recording  tam- 
hour  is  attached  to  the  side  tube  (or  better  the  end)  of  the 
tracheal  cannula  (the  ether  bottle  is  removed,  for  it  is  no 
longer  necessary  as  the  animal  will  then  be  pithed).  The 
other  opening  of  the  tracheal  cannula  carries  a  piece  of 
rubber  tubing  and  a  screw  clamp.  This  clamp  is  used  to 
regulate  the  facility  with  which  air  passes  into  and  out  of 
the  trachea  and  lungs.  This  regulates  the  size  of  the  tam- 
bour stroke  on  the  drum.  Closing  the  clamp  down  in- 
creases the  amplitude  of  the  tambour  stroke;  opening  the 
clamp  decreases  the  stroke.  The  attachment  of  the  tam- 
bour here  and  the  removal  of  the  ether  bottle  can  be  done 
only  after  the  animal  is  pithed. 

When  the  apparatus  is  adjusted  pith  the  animal.  To  do 
this  consult  Figs.  258,  259,  260,  261,  and  262. 

Unfasten  the  dog's  head  and  turn  it  on  the  left  side. 
The  anesthetist  watches  carefully  to  see  that  the  cliest  or 
trachea  is  not  compressed  and  that  the  animal  gets  suf- 
ficient air  ivhile  this  part  of  the  operation  is  performed. 
With  a  scalpel  make  a  median  incision  over  the  slmll  and 
with  large  tin  snips  cut  the  skin  away  in  a  Y-shaped  area 


292 


EXPERIMENTAL   PHARMACOLOGY 


(Fig.  258).  With  a  scalpel  cut  close  to  the  hone  and  dis- 
sect loose  the  right  temporal  muscle.  Keflect  this  upward 
and  hold  it  up  with  forceps.     Take  a  trephine  instrument 


Fig._  258. — Method  of  making  the  first  incision  before  trephining  the  skull.  The 
longitudinal  (mesial)  edge  of  the  opening  is  cut  with  a  scalpel.  The  triangular  piece 
of  skin  and  fascia  is  then  lifted  with  forceps  and   cut  away   with  heavy    (6  inch)    tinner's 

snips. 


o 


Fig.    259. — The    trephine    opening    is    made    about    one-half    to    three-fourths    of    an    inch 
outward  from  the  median  line   to   avoid  the  great  longitudinal  sinus. 


(Fig.  100)  and  ma,ke  an  opening  in  the  skull  (Fig.  259). 
Be  careful  to  avoid  the  longitudinal  sinus — the  opening 
should  he  one-half  to  three-fourths  of  an  inch  away  from 


PITHING    THE    ANIMAL 


293 


the  median  line.  Place  a  wad  of  cotton  in  the  forceps  and 
hold  this  in  the  left  hand  ready  to  cover  the  trephine  open- 
ing.    Pass  a  long  narrow  scalpel  blade  into  the  opening 

K 


^^ 

^P 

f 

■-% 

^^A 

iii^B 

i  ■   '1im 

^w 

^^■^^ASi>^$^la\i. 

1 

^^M 

:ri^S 

^IVV    %BS===S= 

^^^^^^Sl 

Fig.  260. — Method  of  quickly  cutting  across  the  brain  stem  with  a  long  narrow 
bladed  scalpel  while  a  wad  of  cotton  is  held  in  the  forceps  ready  to  crowd  into  the 
trephine  opening  to   check  all  loss  of  blood. 


Fig.  261. — The  cotton  is  held  down  firmly  in  the  trephine  opening  while  a  probe  is 
slipped  in  past  the  cotton  and  is  moved  quickly  and  thoroughly  about  in  a  circular 
manner  to  destroy  every  part  of  the  brain.  If  the  cord  is  also  to  be  destroyed  this  is 
done  by  passing  a  long  fairly  flexible  wire  (one-eighth  inch  soft  brass  rod)  through  the 
trephine  opening  and  out  through  the  foramen  magnum  into  the  spinal  canal.  The  head 
and  neck  may  be  moved  a  little  to  assist  in  passing  the  rod  down  the  spinal  canal  to 
destroy  the  cord. 


and  cut  ciuickly  across  the  brain  stem.  Eemove  the  scalpel 
and  close  the  opening  with  the  cotton.  No  blood  should 
escape.    Into  the  upper  end  of  the  opening  beside  the  cot- 


294 


EXPERIMEISTTAL   PHARMACOLOGY 


ton  pass  a  probe  (Fig.  261)  and  Avith  a  circular  motion  de- 
stroy every  part  of  the  brain.  Kee^D  the  cotton  plugged 
tightly  in  the  opening.  If  it  is  desired  to  destroy  the  cord 
a  one-eighth  inch  soft  brass  wire  slightly  curved  at  the 
end  may  l)e  inserted  past  the  cotton  and  forced  through 
the  foramen  magnum  and  do^A^i  the  spinal  canal.  Bend 
the  animal's  neck  and  head  a  little  to  assist  in  getting  the 
rod  to  enter  the  canal  easily.  Eemove  the  rod,  plug  the 
opening  tightly  with  cotton,  and  replace  the  animal's  head 
into  its  original  position.  Kemove  the  ether  quickly,  the 
animal  will  lie  perfectly  still  and  the  blood-pressure  mil 


Fig.  262. — After  the  brain  (and  cord,  if  desired)  is  destroyed  the  trephine  opening 
IS  plugged  tightly  with  a  wad  of  cotton  forced  in  by  the  hooked  end  of  an  aneurism 
needle.     The  animal's  head  is  then  quickly  returned  to  the  usual  position. 

fall  to  a  height  of  about  three-fourths  to  one  inch  above 
the  base  line  as  seen  on  the  drum. 

If  negative  pressure  is  used  change  to  this  now.  If  pos- 
itive pressure  is  used  attach  the  tambour  and  adjust  all 
writing  points  on  a  slow  drum,  lung  tracing  at  the  top, 
below  this  the  blood-pressure,  and  then  the  base  line  and 
time  signal.  The  lung  tracing  should  have  an  amplitude  of 
about  three  inches.  Be  sure  the  manometer  pointer  will 
pass  up  just  to  the  right  of  the  tambour  pointer. 

Take  one-half  or  one  inch  of  normal  record.  Inject  one 
cubic  centimeter  of  pilocarpine.  Wait  a  little  for  the  ef- 
fect to  develop  ivell.    Then  inject  one-half  cubic  centime- 


PILOCARPINE^    ATROPINE^    MUSCARIXE,    ETC. 


295 


2.  » 
3  ^ 


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W  '5.  o 


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EXPERIMENTAL   PHARMACOLOGY 


ter  of  adrenaline.  Wait — the  blood  circulates  slowly. 
What  do  you  observe?  How  do  you  explain  it?  What 
mechanical  factors  are  concerned!    A  second  contraction 


(ZdM^^^OLXlcfv\. 


Ficj  264— Tracing  shcw'ng  the  action  of  local  (Burroughs,  Wellcome  and  Co.)  on 
the  blo°od-pressure  and  bronchioles  in  a  spinal  dog.  The  animal  had  received  a  dose  ot 
pilocarpine  a  little  while  before  this  tracing  begins  and  the  bronchioles  were  Pfrtially 
contracted  (tonus)  from  the  action  of  the  pilocarpine  which  exercises  a  prolonged  ettect 
on  the   broncho-constrictor   nerve   endings. 

of  the  bronchioles  will  likely  come  on  as  the  effect  of  the 
adrenaline  passes  off.  Wait  for  this  and  give  a  second  in- 
jection of  adrenaline.     (If  the  first  dose  of  pilocarpine  was 


ARECOLINE,  ADRENALINE,  ATROPINE^  ETC.  297 

too  small — this  is  seldom  the  case — then  a  second  may  be 
given  but  this  reduces  the  vitality  of  the  animal  markedly 
and  is  best  avoided.) 

Get  the  animal  into  as  good  condition  as  possible  and 
(take  a  normal)  inject  one  cubic  centimeter  {less  if  the 
animal  is  small)  of  arecoline  solution.  The  response  will 
probably  be  profound.  Wait  for  the  heart  to  beat  slowly 
again.  When  the  bronchioles  are  greatly  constricted  in- 
ject one  cubic  centimeter  of  adrenaline.  Wait  for  the  drug 
to  be  carried  around.  The  result  should  be  striking.  How 
do  you  explain  this?  (If  the  first  dose  of  arecoline  was  too 
small — this  is  seldom  the  case — then  a  second  may  be  given 
but  this  is  best  avoided.) 

Empty  out  the  pilocarpine  {he  sure  the  hull-dog  on  the 
vein  does  not  leak)  and  fill  the  burette  with  atropine  solu- 
tion (one  cubic  centimeter  equals  one  milligram). 

Take  a  normal  record  and  inject  one  cubic  centimeter 
(or  one  and  one-fourth  cubic  centimeters)  of  arecoline. 
When  the  action  is  marked  inject  one  cubic  centimeter  of 
atropine.  Wait  for  the  drug  to  circulate.  What  do  you 
observe?  Explain  all  mechanical  factors.  Inject  one-half 
cubic  centimeter  of  arecoline.  What  conclusions  can  you 
draw? 

Empty  out  the  arecoline  and  fill  the  burette  with  one- 
half  per  cent  barium  chloride  solution.  Barium  acts  pre- 
sumahly  directly  on  the  smooth  muscle  fibers.  Remember 
the  animal  has  had  atropine.  Take  a  normal  record  (the 
animal  will  probably  be  greatly  weakened  by  this  time) 
and  inject  five  cubic  centimeters  of  barium  solution  (three 
cubic  centimeters  if  the  animal  is  small).  What  do  you 
observe?  It  will  take  some  time  for  the  action  to  become 
marked.  Is  the  heart  irregular?  Barium  acts  somewhat 
like  digitalis  and  in  some  respects  resembles  adrenaline. 
Do  the  bronchioles  contract?  If  so  inject  two  cubic  centi- 
meters of  adrenaline.  Do  they  respond  to  this?  Kill  the 
animal  with  a  big  dose  of  barium.    How  does  barium  act  on 


298 


EXPEKIMENTAL   PHARMACOLOGY 


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Fig.  265. — Tracing  showing  the  action  of  arecoline  on  the  rate  of  oxygen  consump- 
tion (and  the  broncho-constriction),  intestinal  contraction,  blood-pressure  and  respira- 
tion in  a   spinal   dog. 


ARECOLINE  AND  ATROPINE 


299 


'-(M.OiAAJicJjL 


SL>  if-t^^^^.C^J^^yU^to-^rySL, 


'^Z^'KrMicA 


Fig.    266. — Tracing    showing    the    action     of    arecoline    and    atropine    on     the     heart 
<myocardiographic   record,    right   auricle   and   left   ventricle)    and   blood-pressure    in   a   dog. 


300  EXPEKIMENTAL   PHARMACOLOGY 

the  heart?  Discuss  in  full  the  action  of  pilocarpine,  areco- 
line  (muscarine),  atropine,  adrenaline  and  barium  on  the 
bronchioles.  What  part  do  the  medullary  centers  play  in 
this  action?  What  is  the  innervation  of  the  bronchioles? 
(See  Dixon  and  Ransom:  Journal  of  Physiology,  1914.) 

EXPERIMENT  LXXI. 
Nicotine.     (Frog:     General  Symptoms.) 

1.  Into  the  anterior  lymph  sac  of  a  frog  inject  one-half 
cubic  centimeter  of  one-half  per  cent  nicotine  solution. 
Place  the  animal  in  a  sink  and  watch  its  actions.  Do  you 
observe  anything  peculiar  about  its  attitude?  When  the 
dose  is  too  large  the  animal  may  die  too  quickly  to  show 
typical  effects.  Make  a  sketch  of  the  position  of  the  limbs 
after  the  action  of  the  drug  becomes  marked.  Watch  and 
See  if  this  stage  passes  off.  Save  the  frog  and  observe  it 
as  often  as  possible  for  several  hours.  Do  you  note  any 
Convulsions  at  any  time?  On  what  structures  does  nicotine 
act  to  produce  these  results? 


EXPERIMENT  LXXII. 

Nicotine.    (Frog:  Heart  and  Vagus  Nerve.) 

1.  Pith  the  frog  and  take  a  normal  heart  record  show- 
ing both  vagus  (trunk)  and  crescent  inhibition.  Pour  two 
drops  of  nicotine  solution  (one  per  cent)  on  to  the  heart. 
Wait  a  few  seconds.  Do  you  get  an  immediate  effect? 
How  do  you  explain  this?  If  there  is  a  change  in  the 
heart  rhythm  does  this  continue  or  is  there  a  return  to 
normal?  Stimulate  the  vagus  and  note  the  effect  on  the 
inhibition  of  the  heart.  How  do  you  explain  this  ?  Stimu- 
late the  crescent.  Explain  your  results.  How  does  nico- 
tine cause  these  two  results?    Is  the  heart  muscle  directly 


ACTIOISr   OF  ]\TICOTINE 


301 


affected?  Apply  more  of  the  drug  and  observe  the  later 
action  on  the  heart.  What  is  the  innervation  of  the  heart 
(Fio;.  222)  ? 


j^^^CXtk^^cLa. 


/V      A./V      /V      A./V/VA./V/V/VA./V/VyV/A./V 


^^a^-<^5^^c^-«^:e<v^JiW-  ^^,<um^^. 


Fig.    267. — Frog    heart    tracing    showing    the    action    of    nicotine.       The    vagus    trunk 
was   stimulated   as   indicated.      In   the    normal    (lower)    tracing   inhibition    occurs   but    after 
nicotine    (second   tracing)    no  inhibition   follows.      How  do   you  explain  this?      Stimulation 
of   the    crescent   in    the   next    two   lines    still    is    followed    by   inhibition.      The    final    effects 
of  the   drug  are   shown   in   the  last   two    (upper)    tracings. 


EXPERIMENT  LXXIII. 

Nicotine.    (Turtle:  Heart  and  Vagus  Nerve.) 

1.  Eepeat  the  above  experiment  on  a  turtle  which  is  a 
more  satisfactory  animal  for  the  experiment  than  is  the 
frog.     Why? 


302  EXPERIMENTAL   PHARMACOLOGY 

EXPERIMENT  LXXIV. 
Nicotine.    (Turtle:    Lungs.) 

1.  Pith  a  turtle,  brain  and  cord.  Remove  the  plastron 
as  shown  in  Fig.  232.  Consult  also  Fig.  233.  Arrange  a 
cannula  in  the  wind  pipe  and  a  small  (very  sensitive) 
tambour  to  write  on  the  drum.  The  magnification  for  the 
writing  point  should  be  large.  Partially  inflate  the 
lungs  (blow  them  up  from  the  air  vent  in  the  tambour 
tube)  and  adjust  the  tambour  on  the  drum.  (A  heart 
tracing  may  be  taken  also  when  the  nerves  are  stimulated, 
but  it  is  difficult  to  get  a  satisfactory  heart  tracing  when 
drugs  are  injected  into  the  heart.  It  is  possible  to  inject 
drugs  into  the  large  vein  running  into  the  liver  but  this  re- 
quires considerable  care  and  when  lung  records  only  are 
wanted  the  heart  is  best  left  alone.) 

Dissect  out  the  vagus  and  sympathetic  nerves  on  one 
side  of  the  neck  and  stimulate  them.  Do  you  get  a  satisfac- 
tory record?  Go  far  down  in  the  tissues  at  the  side  of  the 
neck  and  find  the  sympathetic  branch  which  joins  a  gan- 
glion on  the  vago-sympathetic  nerves.  Stimulate  this 
branch  and  see  if  you  can  get  a  lung  tracing  from  it.  (The 
opposite  lung  may  be  temporarily  shut  off  by  a  bull-dog 
on  the  corresponding  bronchus.) 

After  one  or  two  records  of  the  lung  contraction  follow- 
ing nerve  stimulation  have  been  secured  then  remove  the 
bull-dog  from  the  bronchus,  see  that  botli  lungs  are  mod- 
erately distended  and  that  the  tambour  is  properly  ad- 
justed on  the  drum.  Start  the  drum  and  with  a  fine-pointed 
hypodermic  syringe  inject  into  the  ventricle  one  or  two 
cubic  centimeters  of  one-half  per  cent  nicotine  solution. 
The  circulation  is  sluggish  in  the  turtle  and  some  time  may 
elapse  before  the  drug  reaches  the  lungs.  Wait  for  the 
effect  to  come  on.  Be  sure  the  turtle  is  in  a  satisfactory 
condition  (not  diseased  or  weakened  in  any  way)  and  that 


ACTION   OF   NICOTINE 


303 


304  EXPEElMENTAL   PHARMACOLOGY 

the  heart  beats  welL  A  marked  effect  should  be  produced. 
Explain  the  action  of  the  drug  in  this  case.  It  will  be  in- 
structive if  you  can  compare  the  action  of  nicotine  on  the 
turtle  lung  with  the  corresponding  action  on  a  dog's  lung. 

EXPEKIMENT  LXXV. 

Mcotine,  Arecoline,  Atropine.    (Dog:  Blood-pressure,  Res- 
piration, Limb  Volume,  Intestinal  Oontraction.) 

1.  Etherize  a  dog  and  arrange  for  blood-pressure,  res- 
piration and  intestinal  contraction  (Fig.  246).  Examine  a 
plethysmograph  for  the  hind  limb  of  a  dog  (Fig.  269). 
Eub  soapsuds  around  the  left  hind  leg  close  up  to  the 
body  of  the  animal.     Take  a  razor  and  shave  the  hair  all 


Fig.    269. — Method   of  application   of  a  plethysmograph   to   the   hind  leg   of  a   dog. 

off  in  band  about  one  and  one-half  inches  wide  entirely 
around  the  leg.  (A  strong  solution  of  sodium  sulphide 
may  be  used  to  remove  the  hair  by  rubbing  the  solution 
over  the  selected  area.  The  hair  can  then  be  readily  scraped 
off.  But  this  is  a  filthy  method.  A  cheap  safet}^  razor  is 
best.)  The  hair  must  be  removed  or  the  rubber  band  of 
the  plethysmograph  will  leak  air  around  the  limb.  Attach 
the  plethysmograph  as  illustrated  and  connect  it  to  a  small 
bowled  very  sensitive  tambour.  From  above  down,  the 
records  on  the  drum  should  be — leg  volume,  intestine, 
blood-pressure,  respiration,  base  line  and  time  signal.  In- 
jecting burettes  should  be  placed  in  the  right  femoral  and 
the  left  jugular  veins.  These  contain  nicotine  (one-half 
per  cent)   and  adrenaline. 


ACTION   OF  NICOTUS^E 


305 


Take  a  normal  tracing  (stimulate  the  vagi  and  get  the 
cardiac  effect)  and  then  inject  one  cubic  centimeter  {less 
if  the  animal  is  small)  of  nicotine  solution.  Watch  the  pu- 
pil as  the  drug  is  injected.    What  do  3^ou  observe?    Wait 


Fig.  270. — Tracing  showing  the  action  of  a  fatal  dose  of  nicotine  on  the  blood- 
pressure  and  respiration  of  a  dog  anesthetized  with  nitrous  oxide.  Can  you  see  the 
evidence  of  a  preliminary  stimulation  (followed  by  paralysis)  of  the  cardio-inhibitory 
ganglia? 


for  the  effects  to  pass  off.  What  do  your  records  show 
for  the  intestine  and  leg?  How  can  you  explain  these? 
Inject  one-half  cubic  centimeter  of  adrenaline.  How  does 
this  drug  compare  with  nicotine  in  action?    On  wliat  struc- 


306  EXPERIMENTAL   PHARMACOLOGY 

tures  does  nicotine  act  and  what  is  the  nature  of  this  ac- 
tion? Do  your  records  show  this!  Inject  another  dose  of 
nicotine  of  such  size  as  your  animal  will  probably  tolerate 
well. 

Stimulate  the  vagus  nerve  and  see  how  this  affects  the 
heart.  Do  you  get  an  inhibition!  If  so  give  another  dose 
of  nicotine  and  again  stimulate  the  vagus.  What  are  your 
conclusions'?  How  could  you  prove  this?  Observe  one  pu- 
pil and  stimulate  the  corresponding  vago-swipathetic 
trunk.  Does  the  pupil  contract  or  dilate?  How  do  you  ex- 
plain this?    What  is  the  action  of  nicotine  on  the  pupil? 

Empty  the  nicotine  out  of  the  burette  and  place  arecoline 
solution  (one  cubic  centimeter  equals  one-half  milligram) 
therein.  Inject  one  cubic  centimeter  of  arecoline  {less  if 
the  animal  is  small)  and  get  a  record.  Observe  the  pupil 
as  the  drug  is  run  in.  Has  the  nicotine  affected  the  action 
of  this  drug  in  any  way?  Walt  for  the  drug  to  act.  Inject 
one-half  cubic  centimeter  of  adrenaline  to  revive  the  ani- 
mal (give  a  second  dose  if  necessary.) 

Empty  out  the  adrenaline  and  fill  the  burette  ^vith  atro- 
pine solution  (one  cubic  centimeter  equals  one  milligram). 
Take  a  normal  record  and  then  inject  one  cubic  centimeter 
(or  one  and  one-half  cubic  centimeters)  of  arecoline. 
When  the  action  is  very  marked  inject  one  cubic  centimeter 
of  atropine.  Wait — the  circulation  is  slow.  Do  you  get 
the  proper  response  to  the  drug?  How  do  you  explain  this? 
Inject  one-half  cubic  centimeter  more  of  atropine. 

Empty  out  the  arecoline  and  fill  the  burette  with  nicotine. 
Start  the  drum  and  inject  one  cubic  centimeter  of  nico- 
tine. Does  your  record  corresiDond  with  the  theoretical 
action  of  the  drug  ?  How  do  you  explain  this  ?  A^Tiat  struc- 
tures are  involved?  Kill  the  animal  with  a  large  dose  of 
nicotine.  Discuss  in  full  the  counteraction  of  these  drugs. 
Open  the  chest,  dissect  out  the  left  pulmonary  artery  and 
place  a  ligature  under  it.  (See  Figs.  274,  275,  276,  and 
277.)    Slip  this  ligature  as  far  out  on  the  artery  as  possible 


NICOTINE,    ADRENALINE,    PILOCARPINE  307 

and  tie.  Lift  the  ends  of  the  ligature  up  and  draw  the  lung 
upward  into  view.  Clamp  the  ends  of  the  ligature  to  the 
chest  wall.  Could  you  put  a  cannula  into  the  artery  (as 
shoA^^l  in  the  illustrations)  while  the  heart  Avas  heating  and 
disturhing  your  operations  considerahlyf 


EXPERIMENT  LXXVI. 

Nicotine,  Adrenaline,  Pilocarpine,  Atropine.    (Dog:  Blood- 
pressure,  Intraocular  Pressure,  Respiration  and  Kidney, 
Spleen  or  Intestinal  Loop  Volume.) 

1.  Give  a  dog  a  small  dose  of  chloretone  and  then  ether- 
ize it.  Arrange  for  blood-pressure,  respiration  and  kidney, 
spleen  or  intestinal  loop  volume  records. 

Observe  the  arrangement  of  the  apparatus  showm  in  Fig. 
271.  A  medium  sized  syringe  j)oint  is  thrust  into  the  an- 
terior chamber  of  the  eye  as  shoAvn  in  the  upper  right  hand 
corner  of  the  picture.  The  cornea  is  composed  of  tough, 
dense  tissue  and  the  syringe  point  will  not  leak  around  the 
outside  if  the  needle  is  not  moved  from  side  to  side  after  it 
is  inserted  (at  an  acute  angle)  through  the  cornea.  The 
needle  is  attached  to  a  rubber  tube  which  connects  vdth 
a  water  manometer  (filled  with  normal  salt  solution).  The 
needle  and  the  end  of  the  rubber  tube  are  held  in  a  hole  in  a 
cork  which  is  clamped  in  a  burette  clamp  which  can  be 
brought  close  to  the  eye.  The  manometer  is  filled  ^Yit\l  salt 
solution  from  the  mercury  bulb  and  the  tubes  (washout 
also)  and  needle  are  filled  Avith  the  solution,  a  little  of  the 
solution  being  alloAved  to  run  out  of  the  needle  as  it  is  in- 
serted through  the  cornea.  It  is  advisable  to  use  an  extra 
stand  to  hold  the  needle  (burette  clamp)  close  up  to  the 
eye.  The  amount  of  pressure  in  the  tube  is  regulated  by 
raising  or  loAvering  the  manometer.  The  recording  tam- 
bour should  be  small.  No  fluid  should  be  in  the  tube  lead- 
ing from  the  manometer  to  the  tambour.     The  injecting 


308 


EXPERIMENTAL   PHARMACOLOGY 


burettes  contain  nicotine  (one-half  per  cent)  and  adrena- 
line. Stimulate  the  vagus  nerve  on  the  side  on  which  the 
eye  record  is  being  taken.  What  conclusions  can  you  draw? 
Bring  all  writing  points  on  to  the  drum  and  take  a  nor- 
mal record.  Inject  one  cubic  centimeter  (twelve  kilo  dog. 
less  if  the  animal  is  smaller)  of  nicotine  and  record  the 


Hercury  bulb 

or  funnel 


Fig.   271. — Arrangement  of   apparatus  for  recording  intraocular  pressure. 

result.  Stimulate  the  vagus  nerve  again  and  see  what 
happens.  Explain.  Inject  one-half  cubic  centimeter  of 
adrenaline.  Wait  a  sufficient  time  for  the  results  to  wear 
off.  What  conclusions  can  3^ou  draw?  What  mechanical 
factors  are  involved?    Inject  one  cubic  centimeter  more  of 


ACTION   OF   NICOTINE 


309 


nicotine.     How  does  this  record  compare  with  your  first 

one"?    What  is  the  action  of  nicotine  on  the  heart  muscle  I 

Stimulate  the  vagi  from  time  to  time  and  note  any  change 

in  reaction.    When  an  inhibition  of  the  heart  can  no  longer 


vccu/m/^. 


W.CaA.oCU 


,5^^  1lU6iUL(/%)^ 


Fig.  272. — Tracing  showing  the  action  of  nicotine  on  the  spleen  volume,  blood-pres- 
.'sure  and  respiration  in  a  dog  (etherized).  Compare  this  record  with  one  made  by  ad- 
renaline (or  coniine). 


be  obtained  (inject  more  nicotine  if  necessari/)  then  empty 
ont  the  nicotine  and  fill  the  bnrette  with  pilocarpine  solu- 
tion (one  cubic  centimeter  equals  one  milligram). 

Inject  one  cubic  centimeter  of  pilocarpine.    Wait  for  the 


310  EXPERIMENTAL   PHARMACOLOGY 

drug  to  act.  When  the  effects  are  well  marked  inject  one- 
half  cubic  centimeter  of  adrenaline.  What  conclusions  can 
you  draw  from  your  records'? 

Inject  one-fourth  cubic  centimeter  more  of  adrenaline  (if 
necessary)  to  get  the  animal  into  as  good  condition  as  pos- 
sible. Then  empty  out  the  adrenaline  (save  it)  and  fill  the 
burette  with  atropine  solution  (one  cubic  centimeter  equals 
one  milligram). 

Inject  another  dose  (estimate  the  size  to  get  the  results) 
of  pilocarpine  and  when  the  reaction  comes  on  inject  one 
cubic  centimeter  of  atropine.  Do  you  get  what  you  should 
get?  What  conclusions  can  you  draw!  Stimulate  the  va- 
gus nerve  and  see  if  your  eye  record  is  affected.  What  is 
the  relation  between  the  cervical  vagus  nerve  trunk  and  the 
eye  in  the  dog?  How  does  this  compare  with  a  man!  If 
you  get  any  eye  records  study  and  explain  carefully  the 
exact  cause  of  these  records.  Are  they  due  to  local  or 
remote  actions  of  the  drugs  concerned? 

Empty  out  the  pilocar]Dine  and  put  barium  chloride  solu- 
tion in  the  burette.  Inject  five  cubic  centimeters  (one-half 
per  cent)  of  the  solution.  Obtain  as  good  records  as  you 
can.  Then  inject  sufficient  barium  to  kill  the  animal.  Dis- 
cuss the  action  of  the  drugs  used  in  this  experiment.  Com- 
pare your  results  with  those  obtained  by  other  members 
of  the  class. 

EXPERIMENT  LXXVII. 

Nicotine,  Adrenaline,  Barium.    (Dog:  Pulmonary  Blood- 
pressure,  Carotid  Pressure.) 

1.  Etherize  a  dog  (twelve  or  fourteen  kilos  preferred). 
A  small  dose  of  chloretone  may  be  given  to  some  advan- 
tage. Arrange  for  a  perfectly  reliable  artificial  respira- 
tion (a  power  driven  machine  is  greatly  to  be  preferred). 
Isolate  and  ligate  loosely  both  vagi.  Arrange  to  record 
carotid  blood-pressure.    The  injecting  burettes  contain  nic- 


PULMONARY   BLOOD-PRESSURE 


311 


otine  (one-lialf  per  cent)  and  adrenaline  (1:10,000). 
Place  the  pulmonary  manometer  in  position  on  the  drum. 
Its  base  line  should  be  about  one-half  inch  above  the  ca- 
rotid pressure  and  the  carotid  writing  point  should  l)e  able 
to  pass  up  just  to  the  left  of  both  pulmonary  pointers  (see 
273). 


Fig 


-To  pulley 


Pressure 

bottle-— \ 


-^in.wlre 


Pulmonary 
manometer 
\{mercury  or  salt  sol.) 

■  Cdrotid  manometer 
(mercury) 


Fig.    273. — Arrangement    of    apparatus    for    recording   pulmonary    blood-pressure. 


312 


experimejsttal  pharmacology 


By  a  median  longitudinal  incision  open  the  thorax.    For 
the  method  of  giving  ether  when  the  chest  is  open  see  Figs. 


© 


Loose  licjafure 
pawed  ed^e  of  sternum 

Lefi-  pulmonary  artery 
pulmonary  veins 

Lung,  parHai/y 

inflated 
Pericardium 
oyer  hesrf 

.fVphrenic  nerve 
Snowinci  ower  pericardium 


Fig.  274. — Dissection  showing  the  method  of  lifting  up  the  left  pulmonary  artery 
with  an  aneurism  needle  and  tying  a  ligature  loosely  around  the  artery  far  out  next  to 
the  lung  tissues. 


T.T.H. 


® 


Hemostdt 


First  ligature  tied  and 
fastened  on  wall  of  chest 

Second  loose  liqgture 
-    on  pulmonary  artery 


Fig.  275. — The  first  ligature  is  tied  tightly  (at  the  edge  of  the  lung)  and  with 
a  hemostat  the  end  of  the;  ligature  is  clamped  to  the  edge  of  the  chest  wall  in  such  a 
manner  as  to  lift  up  and  support  the  outer  end  of  the  artery  (and  the  left  lung).  A 
second    (loose)    ligature   is   placed   around   the   artery    ready   to   tie   in    the   cannula. 

53  and  107.    With  four  large  ligatures  tie  the  chest  widely 
open  as  shown  in  Fig.  106. 

Consult  the  Figures  and  seek  for  the  left  pulmonary 


PEELIMINARY    OPERATIONS 


veins.  The  left  pulmonary  artery  lies  just  posteriorly  and 
cephalad  to  the  vein  which  is  nearest  the  apex  of  the  chest. 
Keep  to  the  left  of  the  anterior  mediastinum  if  possible. 


® 


Cut  close  fo  outer 
f/gature 

Bulldoq  on  pulmonary 
artery  close  to  heart 


Fig.  276. — A  special   bull-dog  is  placed  on  the  vessel  near   the   heart   and  a  notch   is 
cut   in   the    artery    close   to    the    outer   ligature    with    the    scissors. 


Disconnected  tube 

fo  manometer 


Cannula  in  position  to  be 
inserted  into 
pulmonary  artery 


Artery  held  open 

with  forceps 


Fig.    277. — Method    of    inserting    the    special    cannula    into    the    artery.       (For    discussion 

see  text.) 

This  keeps  the  heart  on  the  right  side.  It  is  usually  ad- 
visable to  pick  up  the  mediastinum  and  clamp  it  to  the  tis- 
sues at  the  right  sawed  edge  of  the  sternum.    This  securely 


314  EXPEKIMENTAL   PHAEMACOLOGY 

holds  the  heart  over  in  the  right  side  of  the  thorax  and 
thus  gives  a  freer  field  for  the  operation.  With  a  probe 
{blunt  point)  carefully  dissect  loose  the  pleural  (fascia) 
covering  over  the  area  between  the  arch  of  the  aorta  and 
the  adjacent  pulmonary  vein.  Beneath  this  fascial  cover- 
ing you  will  find  the  pulmonary  artery. 

Consult  Fig.  274  and  carefullly  pass  a  large  aneurism 
needle  beneath  the  artery.  Free  as  long  a  space  of  the  ar- 
tery as  you  can  readily  isolate.  This  will  average  about 
three-fourths  of  an  inch.  Pass  a  twine  ligature  around  the 
vessel  and  tie  it  loosely  (Fig.  274).  Now  with  large  for- 
ceps (using  one  finger  to  help  hold  the  twine)  slip  the  liga- 
ture outward  into  the  edge  of  the  left  lung  as  far  as  you 
can  and  then  tie  tightly.  Take  hold  of  the  ligature  and  lift 
up  the  lung  as  far  as  you  can  safely  raise  it,  pass  the 
ligature  out  over  the  chest  wall  and  clamp  it  with  a  hemo- 
stat  to  the  chest  wall.  With  the  aneurism  needle  still  un- 
der the  vessel  pass  a  second  ligature  around  the  artery  and 
tie  it  loosely.  A  iveak-springed,  rounded-edged  bull-dog 
clamp  is  now  placed  on  the  artery  as  near  to  the  heart  as 
possible.  The  loose  ligature  is  placed  just  peripheral  to 
the  bull-dog. 

With  the  aneurism  needle  noAV  lift  the  outer  end  of  the 
vessel  and  cut  it  about  one-half  across  (Fig.  276)  with  the 
scissors.  A¥ith  his  right  hand  the  operator  now  passes 
one  of  the  points  of  the  large  sharp-pointed  forceps  into 
the  lumen  of  the  vessel  and  holds  it  open  (the  aneurism 
needle  is  held  under  the  vessel  with  the  operator's  left 
hand)  while  the  assistant  inserts  the  short,  wide  tip  of  the 
cannula  (Figs.  278  and  279)  into  the  vessel.  The  operator 
and  assistant  (each  using  one  hand)  now  tie  the  loose 
ligature  around  the  vessel  thus  fastening  the  cannula 
in  securely.  It  is  advisable  to  leave  the  washout  tube  on 
the  cannula  while  it  is  being  placed  in  the  vessel  but  the 
manometer  tube  is  best  left  off  until  the  cannula  is  securely 
fastened  in  the  vessel.    This  is  done  on  account  of  the  dif- 


PRELlMIISrARY    OPERATIONS 


315 


ficulty  of  manipulating  so  many  pieces  in  the  chest  at  one 
time.  The  beating  of  the  heart  greatly  increases  the  dif- 
ficulties of  the  operation.  The  artery  has  thin  walls  and  a 
sharp-edged  or  strong-springed  bull-dog  will  sometimes 
quickly  wear  a  hole  in  the  vessel  from  the  constant  rubbing 


To  nanometer 


Fig.  278. 


s>-/br  washout 


pulmonary  art 


Fig.   279. 


Fig.    278. — Special   form   of   separable   pointed   cannula   for   the   pulmonary    artery. 

Fig.  279. — Special  (all-glass)  form  of  cannula  for  the  pulmonary  artery.  The  open- 
ing in  the  point  should  be  about  one-eighth  inch  in  diameter  (the  pulmonary  artery  is 
large). 


316  EXPEEIMENTAL   PHARMACOLOGY 

of  the  ventricle  before  the  manometer  can  be  connected  up. 

The  puhiionary  manometer  should  have  its  o^vn  inde- 
pendent base  line  (which  can  be  a  wire  fastened  to  the 
board  of  the  manometer).  It  is  most  instructive  to  the  stu- 
dent to  use  mercury  in  this  manometer  but  sometimes  wa- 
ter or  salt  solution  is  used  instead.  The  comparison  with 
the  carotid  pressure  is  seen  at  once  if  mercury  is  used. 

Sodium  citrate  solution  is  used  to  prevent  coagulation. 
A  T-tube  placed  in  the  tube  going  do^vn  from  the  pressure 
bottle  permits  each  manometer  to  have  its  own  supply  of 
citrate  solution.  When  the  cannula  and  tubing  are  all  ad- 
justed for  the  pulmonary  pressure  {the  manometer  should 
have  been  fully  adjusted  previously)  then  wash  out  the 
tubes  and  manometer  with  citrate  solution  and  fill  the  tubes 
full  hut  leave  no  'positive  pressure  in  the  tubes.  This-  is  of 
great  hnportance.  To  accomplish  best  results  a  slight  neg- 
ative pressure  in  the  tubes  is  advisable.  To  g^i  this  fill  the 
tubes  and  close  both  pinch  cocks.  Then  open  only  the  one 
on  the  washout.  The  pressure  falls  to  zero  in  the  manom- 
eter. Now  between  the  thumb  and  finger  squeeze  the  tube 
from  the  artery  to  the  manometer.  A  small  amount  of  the 
citrate  solution  runs  out.  Now  close  the  washout  and  let 
go  the  tube.  A  slight  negative  pressure  shows  in  the  ma- 
nometer but  the  tubes  are  full  of  solution  and  no  air  is  left 
in  them. 

Work  rapidly  now  for  the  animal  may  die  soon  and  a 
clot  is  very  liable  to  form  in  the  pulmonary  cannula.  Ad- 
just all  writing  points,  remove  the  pulmonary  bull-dog  and 
take  a  short  normal  tracing.  Inject  one-half  cubic  centi- 
meter of  adrenaline  and  get  a  record.  What  effect  has 
this  on  pulmonary  pressure?  Does  the  pressure  rise 
higher  in  the  right  lung  than  it  does  in  the  left?  Does 
your  experiment  demonstrate  this?  Explain.  What  nerv- 
ous structures  are  involved  in  this  reaction? 

As  soon  as  the  normal  is  reached  inject  a  dose  of  nico- 
tine (three-fourths  cubic  centimeter).    Do  you  get  a  satis- 


PULMONARY   BLOOD-PRESSURE 


317 


factory  record?  How  does  nicotine  affect  the  pulmonary 
blood-pressure?  What  structures  are  involved?  What 
mechanical  factors  are  concerned? 

If  you  get  a  pulmonary  clot  put  on  the  bull-dog  and  wash 


Artery.         ' 


Us. 


,CaA6tui 


^(^^i^V(jLymJL, 


\.C^^  H-StA-crucU.. 


Fig.  280. — Tracing'  showing  the  action  of  adrenaline  on  the  pulmonary  pressure,  kid- 
ney volume  and  blood-pressure  (right  carotid)  in  a  dog.  The  straight  "line  just  below 
the   pulmonary   pressure   tracing  is   the   pulmonary   base   line. 

out  the  blood  but  be  sure  no  positive  citrate  pressure  is  left 
in  the  tubes.  This  is  necessary  because  strong  (five  to  ten 
per  cent)  sodium  citrate  solution  is  very  poisonous  to  the 


318  EXPERIMENTAL   PHARMACOLOGY 

heart  and  a  small  amount  can  easily  pass  back  from  the 
pulmonary  artery  into  the  right  ventricle.  This  may  kill 
the  heart  immediately.  Could  you  use  hirudin  for  this  pur- 
pose!    What  objections  could  you  offer? 

The  average  group  of  students  will  not  get  more  than 
two  good  pulmonary  pressure  records  from  one  dog.  If 
the  animal  is  still  in  suitable  condition  inject  five  cubic  cen- 
timeters of  barium  chloride  solution  (one-half  per  cent). 
What  conclusions  can  you  draw?  In  how  many  ways  may 
drugs  affect  the  pulmonary  blood-pressure?  How  many 
of  these  does  your  experiment  illustrate?  What  differ- 
ences are  there  between  the  systemic  and  pulmonary  cir- 
culation? Historically  which  of  the  systems  was  first  dis- 
covered?   By  whom?    Kill  the  dog  with  a  dose  of  barium. 

EXPERIMENT  LXXVIII. 

Nicotine,     Pilocarpine,     Atropine.       (Dog:       Intraocular 
Nerves,  Salivary  Glands,  Oxygen  Consumption,  Blood- 
pressure  and  Respiration.) 

(For  the  anatomy  of  the  eye,  see  Experiment  CXVII, 

page  394.) 

1.  Give  a  dog  (10  kilos)  a  moderate  or  small  dose  of 
chloretone  and  follow  this  with  ether.  Arrange  to  record 
blood-pressure  and  respiration.  Consult  Fig.  281  and  dis- 
sect out  the  optic  nerve  in  the  right  eye.  (Consult  Experi- 
ment LXIII,  2).  Study  Fig.  281  carefully  and  dissect  out 
the  orbit  until  the  eye  ball  can  be  rolled  around  forward  (in- 
ward) enough  to  bring  the  trunk  of  the  optic  nerve  into 
view.  The  skin  around  the  outer  canthus  should  be  cut 
away  and  sometimes  the  bones  of  the  orbit  must  also  be 
chipped  out  a  little  with  bone  forceps.  Try  to  avoid  dis- 
turbing the  blood  vessels  entering  the  eye  from  behind. 
WTien  the  nerve  is  isolated  place  the  platinum  electrodes 
against  the  nerve  sheath  and,  while  Avatching  the  pupil,, 


INTRAOCULAll    NERVES 


319 


stimulate  the  nerve.  The  pupil  may  dilate  (sympathetic 
libers),  contract  (oculomotor  fibers)  or  remain  stationary 
(both  sets  of  fibers  or  none  of  either).  The  electrodes  are 
moved  a  little  and  the  points  can  be  worked  cautiously  down 
into  the  nerve  trunk.  Stimulate  (for  a  moment  only)  at 
each  new  position  of  the  electrodes,  the  pupil  being  watched 
carefully  all  the  time.  At  some  point  in  the  stimulation  the 
pupil  will  show  a  marked  contraction  at  once.  This  is 
striking  when  properly  done  and  will  be  well  worth  the 
time  necessary  to  do  the  dissection  within  the  orbit  with 
especial  care.    Let  each  member  of  the  group  see  the  con- 


Fig.  281. — Method  of  dissecting  out  the  orbital  fat  and  fascia  to  expose  the  optic 
nerve.  The  position  of  the  electrodes  for  stimulating  the  third  nerve  tibers  is  shown. 
The   eye-ball   is    rolled    forward    (inward)    somewhat   to    bring   the    optic    sheath    into   view. 

traction  and  keep  the  observation  in  mind  to  check  your 
later  results. 

Now  turn  the  dog's  head  back  into  the  usual  position 
and  insert  a  cannula  into  AYliarton's  duct.  Stimulate  the 
chorda  tympani  nerve  and  obtain  a  normal  secretion. 

Arrange  the  apparatus  for  recording  oxygen  consump- 
tion and  if  necessary  put  a  small  amount  of  ether  into  it 
(but  avoid  the  ether  if  you  can).  Into  the  femoral  veins 
place  injecting  cannulas,  the  burettes  to  which  contain  nico- 
tine (%%)  and  adrenaline.  Take  some  normal  record  (in- 
cluding at  least  one  or  two  notches  of  the  oxygen  record). 


320  EXPEEIMENTAL   PHARMACOLOGY 

A  good  nicotine  solution  can  often  be  made  by  scraping 
out  the  contents  of  the  bowls  and  stems  of  two  or  three 
tobacco  pipes.  The  material  is  dissolved  in  salt  solution 
and  filtered  before  being  placed  in  the  burette  for  injec- 
tion.   The  results  are  often  striking. 

Inject  a  dose  of  nicotine  (perhaps  three-fonrths  of  a 
cubic  centimeter.  This  will  vary  with  the  size  of  the  ani- 
mal and  also  Avith  the  quality  of  the  drug  as  usually  ob- 
tained in  the  open  market).  Watch  the  pupils  (both)  as 
the  drug  is  injected.  Do  you  get  a  typical  blood-pressure 
record!  If  it  seems  necessary  inject  some  adrenaline  to 
help  restore  the  animal  (watch  the  pupils  as  the  drug  is 


Fig.    282. — Bone    cutting    forceps. 

injected).  What  did  your  oxygen  record  show?  On  what 
does  this  depend?  Inject  another  dose  of  nicotine  (esti- 
mate the  size  to  suit  the  tolerance  of  your  animal).  Stimu- 
late one  vagus  nerve  and  see  if  the  heart  is  inhibited.  If  it 
is,  give  a  little  more  nicotine  cautiously.  Stimulate  the 
chorda  tympani  and  see  if  secretion  follows.  When,  on 
stimulation,  the  vagus  no  longer  can  inhibit  the  heart, 
empty  out  the  nicotine  and  fill  the  burette  Avith  pilocarpine 
solution  (one  cubic  centimeter  equals  one  milligram). 
Substitute  atropine  for  the  adrenaline  in  the  other  burette. 
Inject  one  cubic  centimeter  of  pilocarpine.  What  action 
has  this  on  the  salivary  secretion  and  heart!  Have  you 
injured  the  vessels  going  to  the  salivary  glands?  Wait  a 
little  and  if  the  animal  Avill  tolerate  it  Avell  inject  another 


PlLOCARPllSrE  AND  ATKOPINE  321 

dose  of  pilocarpine.  AVait  for  the  action  of  the  drug  to 
become  well  developed.  How  is  the  heart  affected  ?  Stimu- 
late one  vagus  nerve  and  see  if  this  slows  or  accelerates 
the  heart.  If  it  beats  faster  or  if  the  pressure  rises  how 
do  you  explain  the  result?  Is  this  a  natural  phenomenon 
or  have  the  drugs  caused  it  in  some  Avay?  When  the  action 
of  pilocarpine  is  well  marked  (give  more  of  the  pilocarpine 
if  absolutely  necessary)  inject  one  cubic  centimeter  of 
atropine  solution  (one  cubic  centimeter  equals  one  milli- 
gram). Do  you  get  typical  results  on  the  heart  and  blood- 
pressure  f  Stimulate  the  chorda  tympani  and  see  if  secre- 
tion follows.  Another  smaller  dose  of  atropine  may  be 
given  if  the  animal  will  probably  tolerate  it  well. 

Now  stimulate  the  oculomotor  nerve  again  and  see  if 
you  get  a  contraction  of  the  pupil.  Stimulate  the  vago- 
sympathetic in  the  neck  and  see  if  the  pupil  dilates.  If 
time  permits  dissect  out  the  oculomotor  nerve  on  the  left 
side  and  stimulate  it  to  see  if  contraction  of  the  pupil  will 
occur.  Kill  the  animal  with  a  big  dose  of  atropine.  If 
3^ou  do  not  have  enough  solution  to  do  this  (how  much  does 
it  take?)  then  inject  nicotine  in  addition.  Examine  the 
respiratory  tracing  just  after  the  pilocarpine  was  injected. 
Do  you  note  a  decrease  in  the  amplitude  of  the  respiration 
with  some  difficulty  in  either  expiration  or  inspiration? 
How  do  you  account  for  this  ?  Is  it  central  or  peripheral  f 
How  did  the  atropine  affect  this?  Did  the  atropine  act 
centrally  or  peripherally?  Could  3^ou  obtain  such  phe- 
nomena as  this  in  an  animal  whose  head  had  been  removed 
from  the  body? 

After  the  animal  is  dead  pick  up  one  vago-sympatlietic 
nerve  trunk  in  the  neck  and  follow  it  up  toward  the  base 
of  the  skull.  Dissect  out  the  superior  cervical  ganglion 
and  determine  its  relations  to  the  surrounding  structures. 
From  this  ganglion  sympathetic  fil)ers  pass  to  the  various 
organs,  glands,  involuntary  muscles,  etc.,  of  the  head.  (See 
Fig.  243.) 


322  EXPERIMENTAL   PHAEMACOLOGY 

EXPERIMENT  LXXIX. 

Lobeline.    (Frog  or  Turtle:    Heart  and  Inhibitory  Nerves.) 

1.  Pith  a  frog  or  turtle  and  take  a  heart  tracing  includ- 
ing both  vagus  and  crescent  stimulation  records.  Make  up 
a  solution  of  lobeline  sulphate  containing  approximately 
one  milligram  of  the  drug  to  one  cubic  centimeter  of  dis- 
tilled water.  Lobeline  sulphate  is  a  dark,  thick,  viscid  sub- 
stance and  is  difficult  to  weigh  or  measure  but  dissolves 
readily  in  water. 

While  taking  a  record  on  the  drum  pour  a  few  drops  of 
the  solution  on  the  heart.  Do  you  note  any  immediate 
action?  Stimulate  the  vagus  nerve  and  note  the  action  on 
the  heart.  Now  stimulate  the  crescent  and  see  if  you  ob- 
tain the  usual  result.  What  conclusions  can  you  draw? 
Have  you  obtained  similar  results  with  any  other  drug? 
Could  you  prove  your  conclusions  in  any  other  way?  Ap- 
ply more  of  the  drug  to  the  heart  to  see  the  later  results. 
How  does  lobeline  act?  (See  Edmunds :  American  Journal 
of  Physiology,  xi,  p.  79.) 

EXPERIMENT  LXXX. 

Lobeline,  Pilocarpine.    (Turtle:    Lung  Tracing.) 

1.  Arrange  a  turtle  for  taking  lung  tracings  (consult 
Experiment  LXXIV,  1).  When  all  adjustments  are  made 
take  one-half  inch  of  the  normal  (quiescent)  record  and 
then  inject  into  the  ventricle  with  a  very  fine-pointed  hypo- 
dermic syringe  one  or  two  cubic  centimeters  of  lobeline 
solution  (one  cubic  centimeter  equals  one-half  milligram). 
Do  not  disturb  the  lung  tracing  by  manipulating  the  heart 
carelessly.  Do  you  get  a  satisfactory  lung  record?  How 
do  you  explain  this  action  of  the  drug  ?  On  what  structures 
does  lobeline  act?    Where  are  these  structures  located  in 


LOBELINE,    AKECOLINE,    ATROPIISJ'E 


323 


•-I   «,  -I 
„  o  cr? 


ft 


P   H 


B-3- 


324 


EXPERIMENTAL   PHARMACOLOGY 


the  turtle  1    Do  you  have  any  evidence  that  these  structures 
exist  in  the  turtle? 

As  soon  as  the  curve  returns  to  normal  prepare  to  in- 


^^ 


\\\m\\m\mMm 


Fig.    284. — Turtle    lung    tracing   showing    the    action    of   lobeline. 


MatJi 


I  I  I  1 1  1 1  I  n  I  n  i  n  n  nrfiTTn 


Fig.    285. — Turtle   lung   tracing   showing   the   action    of   lobeline. 

ject  pilocarpine  (one  cubic  centimeter  equals  one-half  mil- 
ligram). The  heart  may  not  be  beating  very  strongly  and 
if  this  is  the  case  it  may  be  advisable  to  Avait  a  few  minutes 
for  the  heart  to  recover.    A  few  drops  of  a  dilute  (1 :10,000) 


LOBELINE,  PILOCARPINE,  ADREXALIXE 


325 


adrenaline  solution  may  be  poured  on  the  heart  to   ad- 
vantage. 

Prepare  to  take  a  second  record  and  then  inject  one  or 
two  cubic  centimeters  of  pilocarpine  solution  into  the 
heart.  Wait  for  the  drug  to  act  as  the  heart  may  be 
slowed  or  stopped  and  the  solution  may  not  reach  the  lung 
tissues  for  some  time.  Do  you  get  a  satisfactory  record? 
How  do  you  explain  this!  On  what  structures  does  pilo- 
carpine act?  Do  you  have  any  evidence  that  such  struc- 
tures exist  in  the  turtle's  lungs!  What  general  conclu- 
sions can  you  draw  from  the  experiment? 


Fig.   286. — Turtle  lung  tracing  showing  the  action  of  pilocarpine. 


EXPERIMENT  LXXXI. 

Lobeline,  Adrenaline,  Pilocarpine,  Tetramethylammonium 

chloride.    (Dog:    Bladder  Contraction,  Blood-pressure, 

Respiration,  Pupil.) 

1.  Arrange  an  eight  kilo  dog  (the  animal  may  be  given 
a  small  dose  of  chloretone — 150  milligrams  per  kilogram 
of  Aveight)  for  recording  blood-pressure,  bladder  contrac- 


326 


EXPERIMENTAL   PHARMACOLOGY 


aMnA.  3.r^,aA^l^i^/0<^'-ML^\^'}^^^&>^- 


ifcSBI^EiiH 


Fig.  287. — Tracing  showing  the  action  of  lobeline  (three  injections)  and  heroine  on 
the  bladder,  bronchioles  and  blood-pressure  in  a  spinal  dog  that  had  previously  received 
3   milligrams   (intravenously)   of  atropine. 


ACTION  OF  LOBELINE 


327 


Fig.  288. — Tracing  showing  the  action  of  lobeline  (two  injections)  on  the  bladder, 
bronchioles  and  blood-pressure  in  a  spinal  dog  which  had  previously  received  a  sufficient 
amount  (135  mgs. )  of  heroine  to  render  the  animal  insusceptible  to  the  specific  action 
oi  the  drug  on  the  bladder  and  bronchioles.  Evidently  here  the  first  dose  of  lobeline 
produced    ganglionic   paralysis   as    shown    by    failure    of    response    to    the    second   dose. 


328  EXPERIMEISTTAL    PHARMACOLOGY 

tions,  and  respiration.  Isolate  and  ligate  loosely  both  vagi 
nerves.  Stimulate  one  and  watch  the  corresponding  pupil- 
lary^ response.  Keep  this  in  mind  for  later  comparisons. 
The  three  injecting  burettes  contain  lobeline  (one  cubic 
centimeter  equals  one-half  milligram),  adrenaline  (1:10,- 
000)  and  pilocarpine  (one  cubic  centimeter  equals  one  mil- 
ligram). 

Take  one  inch  of  normal  tracing.  The  bladder  record 
(leave  space  for  an  upward  contraction)  should  be  on  the 
upper  part  of  the  drum;  below  this  are  the  blood-pressure, 
respiration  and  base  line  in  succession.  Be  sure  the  blad- 
der tambour  and  manometer  pointer  will  just  pass  each 
other  on  the  drum  (the  tambour  to  the  left).  AYhen  all  is 
ready  watch  both  pupils  closely  and  inject  one-half  cubic 
centimeter  of  lobeline  solution.  There  should  be  an  im- 
mediate and  profound  response.  Do  the  pupillary,  blad- 
der and  vascular  responses  all  correspond?  On  what  ana- 
tomical structures  does  the  drug  act  to  produce  each  of 
these  reactions?  Could  ^''ou  find  these  structures  in  a  dis- 
section of  the  animal!  Allow  the  animal  to  return  to  nor- 
mal. 

Inject  one-fourth  cubic  centimeter  of  lobeline.  Do  you 
get  a  response  corresponding  to  that  produced  by  the  first 
dose  of  the  drug!  Hoav  do  you  explain  this!  Could  you 
prove  the  truth  or  falsity  of  your  conclusions !  How  would 
you  do  this!  When  the  records  return  to  normal  inject 
one  cubic  centimeter  of  pilocarpine  solution.  What  is  the 
action  of  pilocarpine  after  lobeline!  Do  these  drugs  coun- 
teract each  other  in  any  respect!  Do  your  records  show 
this!  Explain  the  results  fully.  Inject  a  second  dose  of 
pilocarpine  if  necessary  to  get  satisfactory  records. 

Inject  one-half  cubic  centimeter  of  adrenaline  and  see 
if  the  lobeline  and  pilocarpine  have  changed  the  response 
of  the  animal  to  the  adrenaline  in  any  way.  A¥atcli  the 
pupils  closely  as  the  adrenaline  is  injected.  Now  stimulate 
each  vagus  nerve  and  see  how  the  heart,  blood-pressure 


TETRAMETHYLAMMONIT  ■  M    CM  I.ORIDE 


329 


Fig.  289. — Blood-pressure  (and  kidney  volume)  tracing  showing  tlie  action  of 
tetramethylammonium  chloride  before  and  after  the  injection  of  atropine.  The  first 
dose  of  tetramethylammonium  chloride  caused  a  great  fall  in  pressure  because  the  vagus 
endings  in  the  heart  were  intact.  The  second  dose,  however,  following  paralysis  of  the 
vagus  endings  by  atropine,  caused  a  great  rise  in  pressure.  The  kidney  volume  also 
actiz'cly   shrinks.      To   what   is   this   action  due? 


330 


EXPERIMENTAL   PHARMACOLOGY 


and  pupils  are  affected.  Is  the  respiration  changed  by  the 
stimulation  ?  Have  any  of  these  phenomena  been  influenced 
in  any  way  by  the  drugs  If  so,  what  anatomical  struc- 
tures were  involved  and  how  were  they  affected?  Are 
these  structures  ever  involved  in  pathological  conditions 


eHK<uL<Jjt/u 


Fig.  290. — Tracing  showing  the  action  of  tetramethylammonium  chloride  on  the  blood- 
pressure  and  bladder  contractions  in  a  dog  which  had  previously  received  a  dose  of 
atropine.     Animal   anesthetized  by  nitrous   oxide. 

such  as  typhoid  fever  or  pneumonia?  What  symptoms 
would  these  reactions  probably  produce  in  a  non-anesthe- 
tized animal! 

If  the  animal  is  still  in  suitable  condition  empty  out  the 
pilocarpine  and  fill  the  burette  with  a  solution  (one  cubic 


PILOCARPINE,    TETRAMETHYLAMMONIUM    CHLORIDE         331 


Fig.  291. — Tracing  .showing  the  action  of  pilocarpine,  tetramethylammonium  chloride 
(two  injections)  and  adrenaline  on  the  bronchioles  and  blood-pressure  in  a  spinal  dog. 
Note  the  peculiar  combination  of  cardio-inhibition  and  vaso-constriction  produced  by  he 
tetramethylammonium  chloride  which  also  dilates  the  bronchioles,  while  pilocarpine,  which 
likewise  causes  cardio-inhibition,  produces  contraction  of  the  bronchioles.  Adrenaline 
has  still  a  different   action.      How   do   you   explain   these  various  phenomena? 


332  experimej^tal  pharmacology 

centimeter  equals  one  milligram)  of  tetrametliylammo- 
ninm  chloride.  Inject  one  cubic  centimeter  and  determine 
what  action  this  drug  has  after  lobeline.  What  structures 
are  affected  by  the  drug  and  how  are  they  influenced  f  Kill 
the  animal  with  a  big  dose  of  the  tetramethylammonium 
chloride.  Was  the  bladder  contracted  before  the  last  drug 
was  injected?  If  so,  you  may  miss  part  of  the  action  of 
the  drug. 

EXPERIMENT  LXXXII. 

Lobeline,  Nicotine,  Pilocarpine.    (Guinea  Pig,  Cat,  Dog,  or 
Rabbit:    Uterus  Strip.) 

(Consult  also  the  following  experiment.     One  animal  may 
be  used  for  both  experiments.) 

1.  Examine  carefully  the  apparatus  shown  in  Fig.  292. 
(Consult  also  Fig.  316).  This  simi^le  arrangement  is  suf- 
ficient for  ordinary  qualitative  results  but  the  more  elab- 
orate apparatus  should  be  used  for  especially  important 
experiments  such  as  drug  assaying  by  the  uterine  strip 
method. 

The  animal  used  in  this  experiment  may  often  be  ob- 
tained from  another  group  of  students  who  have  alread}^ 
performed  another  experiment.  It  is  important  to  save  as 
many  animals  as  possible.  If  a  dog  or  cat  is  used  it  must 
first  be  etherized,  then  one  horn  of  the  uterus  (including 
the  ovary)  is  dissected  out  very  carefully  so  as  not  to  in- 
jure the  tissues.  From  this  a  small  uterine  strip  is  pre- 
pared and  with  a  bent  pin  hook  one  end  of  the  uterine  strip 
is  attached  to  the  lower  end  of  the  bent  glass  tube  as  shown 
in  the  picture.  By  another  pin  hook  and  a  small  thread  the 
upper  end  of  the  tissue  is  attached  to  the  short  arm  of  the 
heart  lever.  The  lever  is  weighted  on  the  long  end  by  a 
(movable)  bull-dog  clamp.  If  a  guinea  pig  is  used  (and 
these  animals  are  very  satisfactory)  it  may  first  be  anes- 


UTERINE  STRIP  REl'ORDS  ooo 

tlietized  or  its  head  may  be  instantly  cut  off  witli  a  hatchet 
or  sharp  hand  ax.  The  animal  may  be  anesthetized  with 
iiiti'ous  oxide  (see  Experiment  VII)  if  it  can  be  killed  in  a 
few  seconds  after  it  is  removed  from  the  large  bottle. 
Ethyl  chloride  may  also  be  used  instead  of  ether. 

As  soon  as  the  uterine  strip  is  adjusted  in  the  beaker, 
warm  (38°)  normal  salt  solution  (or  Locke's  solution,  etc.) 


Fio 


292. — Arrangement   of  apparatus   for   recording  contractions   from   a   uterine   strip,   or 
from  an  arterial   ring,  ureter  ring,   intestinal  strip,   ring  of  frog's   stomach,   etc. 


is  placed  in  the  beaker.  The  writing  point  of  the  lever  is 
brought  on  to  the  drum  which  is  started  at  the  slowest 
speed.  Small  rhythmic  contractions  should  be  recorded. 
When  sufficient  normal  records  have  been  taken  (there  are 
great  variations  in  the  normal  contractions  exhibited  by 
different  uteri)  then  with  a  pipette  pour  one  or  two  (or 
more)  cubic  centimeters  of  a  solution  of  lobeline  (one 
cubic  centimeter  equals  one  milligram)    into    the    beaker. 


334  EXPEKIMEE"TAL   PHARMACOLOGY 

The  oxygen  should  be  bubbling  slowly  but  constantly 
through  the  solution.  This  serves  not  only  to  oxygenate 
the  solution  but  also  stirs  it.  Do  you  get  a  response  to 
the  lobeline?  How  do  you  explain  the  result?  After  a  few 
minutes  slip  the  lower  beaker  out  and  replace  the  upper 
one  by  another  containing  fresh  warm  salt  solution.  How 
does  the  uterine  strip  respond  to  this?  Take  some  more 
normal  tracings  and  then  pour  one  or  two  (or  more)  cubic 
centimeters  of  nicotine  solution  (one  per  cent)  into  the 
beaker.  Discuss  your  results  fully.  Change  the  beaker 
again  replacing  it  with  one  containing  fresh  warm  salt 
solution.  Get  some  more  records  and  then  pour  a  small 
amount  of  pilocarpine  solution  (one  cubic  centimeter  equals 
two  milligrams)  into  the  beaker.  Discuss  the  results  in 
full.  Add  some  atropine  solution  to  the  beaker  and  see  if 
this  affects  the  uterine  strip.  (The  size  of  the  ''dose"  of 
the  drugs  used  in  this  experiment  may  have  to  be  varied 
a  great  deal  in  different  experiments.  The  doses  here 
given  will  often  be  too  large  but  the  student  can  test  this 
out  for  himself.) 

EXPERIMENT  LXXXIII. 

Adrenaline,  Lobeline,  Nicotine,  Pilocarpine,  Atropine. 

(Guinea  Pig,  Rabbit,  Dog,  Cat,  Frog: 

Intestinal  Segment.) 

.  (Consult  the  previous  experiment  to  save  animals.) 

1.  Repeat  the  above  experiment  using  a  small  ring  cut 
from  the  small  intestine  of  one  of  the  above  mentioned  ani- 
mals. Do  not  injure  the  intestine  if  it  can  be  avoided  in 
making  your  dissection.  Be  sure  the  intestinal  ring  is 
properly  weighted  (try  different  weights  to  select  the  right 
one)  and  then  record  some  normal  contractions.  Add 
some  adrenaline  (1:10,000)  to  the  beaker  and  record  the 
results.    How  do  you  explain  this?     Change  solutions  and 


LOBELINE,  ADRENALINE^  NICOTINE,  ETC. 


335 


when  normal  contractions  again  occur  add  some  lobeline 
solution  to  the  beaker.  Explain  the  results.  If  a  contrac- 
tion is  produced  counteract  this  by  adding  adrenaline  to 
the  beaker.  Eepeat  this  process  with  nicotine  and  pilo- 
carpine.    (It  may  be  necessary  to  use  a  fresh  ring  of  in- 


C^cr7'iJt^UXJcticn^\ 


v%^V,a;^.M/X.^ 


x/££- 


^11^   '\ 


Fig.   293. — Tracing  showing  the  action  of  muscarine   on  intestinal   contractions,    respiration 
and  blood-pressure   in   a   dog. 


336  EXPERIMENTAL   PHARMACOLOGY 

testine.)  Again  add  pilocarpine  to  the  beaker  and  if  a 
contraction  is  produced  then  add  atropine  sohition  (one 
cubic  centimeter  equals  five  milligrams).  Do  you  obtain 
satisfactory  results!  State  in  full  your  conclusions.  Add 
some  barium  chloride  (one-half  per  cent  solution)  to  the 
beaker  and  note  the  results. 

A  part  or  all  of  the  experiment  may  be  repeated  by  us- 
ing a  longitudinal  strip  of  the  small  intestine.  What  effect 
does  adrenaline  have  on  longitudinal  strips!  What  is  the 
innervation  of  the  small  intestine!     (Fig.  318). 

The  experiment  ma}^  be  repeated  using  a  ring  of  tiie 
stomach  of  a  frog. 


EXPERIMENT  LXXXIV. 
Muscarine,  Atropine.    (Turtle:    Lung  Tracings.) 

1.  Prepare  a  turtle  for  taking  lung  tracings.  Inject  into 
the  heart  one  or  two  cubic  centimeters  of  muscarine  solu- 
tion (one  cubic  centimeter  equals  one-half  milligram)  and 
record  the  result.  Do  3^ou  get  a  contraction  of  the  lungs  I 
How  do  you  ex]Dlain  your  results!  Is  the  heart  beating 
well!  Inject  one  or  two  cubic  centimeters  of  atropine  solu- 
tion (one  cubic  centimeter  equals  one-half  milligram).  Do 
you  get  a  contraction  or  a  relaxation  of  the  lungs !  How  do 
you  explain  the  results !  Perhaps  you  may  want  to  repeat 
the  injection  of  atropine  on  a  second  turtle.  How  do  your 
results  compare  with  those  obtained  in  a  dog  or  cat! 

If  the  lungs  relax  after  a  contraction  can  the  relaxation 
be  recorded  if  the  weight  of  the  liver  and  intestines  is  rest- 
ing on  the  pulmonary  sacs !  Could  you  modify  the  experi- 
ment to  advantage  in  any  way!  It  is  usually  advisable  to 
dissect  out  the  liver  and  intestines  and  most  of  the  skeletal 
muscles  before  trying  to  record  lung  contractions.  Do  not 
injure  the  vessels  going  to  the  lungs. 


Serosa 

tluscularis 
Circular  fibers^ 
Longitudinal 
fibers 

5ubmuco5a 
Muscularis  IJ 
mucosdU 
mi  and     V*. 

Lymphgland  ^ 


motor 


Vagus  fiber5    {.,^^,;^;^^,y 


"^^^^s^Auerbach's  plexus 

(between  muscle  layers) 

^^Meis5r)er's  plexus 

in  submucosa ) 

^—\\-~    Preganglionic 


^  rPostganglionic  fiber 

-5ympatheHc  fiber 

{inhibitory) 

—Blood  vessels 


Fig.   294. — Diagrammatic   cross-section   of   the   intestine    (small)    to  show   the   manner   of  its 
innervation.      See   also    Fig.   318. 


ACTIOX    or    PHYSOSTIGMIXE 


337 


EXPERIMENT  LXXXY. 
Physostigmine.     (Frog:    Heart  Tracing.) 

1.  Pith  a  frog  and  obtain  heart  tracings  showing  the  ac- 
tion of  physostigmine  (eserine).  The  salicylate  of  eserinc 
is  the  best  salt  to  nse,  the  sulphate  is  deliquescent — one 
cubic  centimeter  equals  one  milligram.  The  solutions 
should  be  freshly  prepared  for  each  experiment. 


Fig.  295. — Turtle  heart  tracing  showing  the  action  of  nicotine,  arecoline  and  atro- 
pine. At  the  places  marked  R.V.S.,  the  right  vagus  nerve  was  stimulated.  Before 
nicotine  inhibition  is  produced  but  this  is  absent  after  the  drug  is  applied.  Note  the 
temporary  slowing  of  the  heart  immediately  following  the  application  of  the  drug.  How 
do  you  explain  this?  The  beat  again  becomes  rapid  but  arecoline  slows  it  while  atropine 
causes  a  return  of  the  normal   rate.      Explain  the  actions. 

Does  the  drug  have  any  action  on  the  inhibitory  appa- 
ratus of  the  frog?     Compare  this  ^Yit\l  pilocarpine. 


EXPERIMENT  LXXXVI. 

Physostigmine,  Atropine,  (Sodium  Nitrite.     (Frog: 
Stomach  Ring.) 

1.  Prepare  a  ring  of  the  stomach  of  a  frog  and  arrange 
it  in  the  manner  shown  in  Fig.  292  for  recording  contrac- 
tions on  the  drum.    Is  the  muscle  vum  already  in  a  state  of 


338  EXPERIMENTAL   PHARMACOLOGY 

strong  tonic  contraction?  If  it  is,  can  it  contract  any 
further?  Adjust  the  weight  and  pour  into  the  beaker  one 
or  two  cubic  centimeters  of  eserine  solution.  (Add  more 
drug  if  necessary.)  What  conclusions  can  you  drawl  Add 
some  atropine  to  the  beaker  and  note  the  results. 

The  experiment  may  be  repeated  (a  fresh  stomach  ring 
may  be  needed)  and  after  the  eserine  action  has  been  well 
developed  sodium  nitrite  solution  (one-half  per  cent — a 
few  cubic  centimeters)  can  be  added  to  the  beaker.  What 
do  you  observe?  What  conclusions  can  you  draw?  On 
what  structures  and  in  what  manner  does  each  drug  act? 
Of  what  clinical  significance  is  each  of  these  actions? 

EXPERIMENT  LXXXVII. 

Physostigmine.     (Turtle:    Heart  Tracing.) 

1.  Repeat  Experiment  LXXXV  using  a  turtle  instead  of 
a  frog.  Does  the  drug  act  in  any  way  on  the  crescent 
ganglia  or  the  post  ganglionic  fibers?  Compare  this  with 
nicotine  and  arecoline. 

EXPERIMENT  LXXXVIII. 

Physostigmine,  (Adrenaline,  Atropine).     (Turtle: 
Lung  Tracing.) 

1.  Arrange  a  turtle  for  recording  lung  tracings  and  then 
inject  into  the  heart  one  or  two  cubic  centimeters  of  eserine 
solution  (one  cubic  centimeter  equals  one-half  milligram). 
What  action  has  the  drug  in  this  case?  Is  this  a  ganglionic 
or  nerve  ending  reaction?  Could  you  prove  your  conclu- 
sion? Now  make  a  second  injection  of  eserine  into  the 
heart  (if  it  has  not  already  become  too  weak  or  stopped) 
and  follow  this  with  an  injection  of  adrenaline  (1:1000). 
Atropine  may  be  used  instead  of  adrenaline  (or  better  a 
second  experiment  on  a  fresh  animal  may  be  performed). 


PHYSOSTIGMINE,    HYOSCINE,    ADREN^ALINE  66\) 

What  conclusions  can  you  draw?  Do  atropine  and  adren- 
aline act  on  the  lungs  of  the  turtle  in  the  same  way  that 
they  do  on  the  dog's  lungs  I  Could  you  prove  your  conclu- 
sions^ 

EXPEEIMENT  LXXXIX. 

Physostigmine,   Hyoscine,   Adrenaline,    (Trimethylamine). 

(Dog:    Respiration,  Blood-pressure,  Intestinal 

Contractions.) 

(See  following  experiment.) 

1.  Arrange  a  dog  (a  cat  or  rabbit  may  be  used)  for 
recording  blood-pressure,  respiration,  and  intestinal  con- 
tractions. (For  the  latter  purpose  use  the  finger  cot,  cathe- 
ter, burette,  and  tambour  method.)  The  three  injecting 
burettes  contain  physostigmine  (one  cubic  centimeter 
equals  one-half  milligram),  hyoscine  (one  cubic  centimeter 
equals  one  milligram — atropine  or  hyoscyamine  may  be 
substituted — could  you  use  homatropine?)  and  adrenaline 
(or  trimethylamine  hydrochloride — one  cubic  centimeter 
equals  one  milligram). 

Take  a  normal  record  and  then  inject  two  cubic  centi- 
meters (for  a  cat  or  rabbit  one-half  cubic  centimeter)  of 
physostigmine.  How  is  the  respiratory  tracing  affected? 
Do  you  get  normal  results  from  the  heart  and  intestine? 
Was  the  dose  too  large  or  too  small?  The  instructor  may 
be  able  to  advise  you  on  this  point,  because  he  can  observe 
the  action  of  the  same  drug  solution  you  are  using  in  the 
experiments  performed  by  other  members  of  the  class.  As 
soon  as  the  action  of  the  eserine  becomes  well  marked  in- 
ject a  dose  (one-half  cubic  centimeter  for  a  dog)  of 
adrenaline  (or  trimethylamine,  one  cubic  centimeter). 
What  action  has  this  on  the  respiration?  Does  it  counter- 
act the  eserine?  Explain  the  relations  of  these  two  drugs 
to  the  respiration  both  centrally  and  peripherally.    How  is 


340 


EXPERIMENTAL   PHARMACOLOGY 


the  eserine  intestinal  reaction  affected  by  adrenaline? 
What  structures  are  involved  and  how  are  they  affected? 
What  is  the  innervation  of  the  intestine?  Would  it  be  ad- 
visable for  a  physician  to  understand  this  innervation? 
How  could  he  best  learn  the  nervous  control  of  the  intes- 
tinal movements? 


Fig.  296. — Tracing  showing  the  action  of  trimethylamine  on  the  bronchioles  and 
blood-pressure  of  a  spinal  dog.  The  bronchioles  were  in  a  state  of  moderate  contrac- 
tion from  the  effects  of  a  dose  of  pilocarpine  at  the  beginning  of  the  tracing.  Record 
made   by  aspiration   of   the   chest.      (See   IJ.xperiment  lyXX.) 

Wait  till  the  animal  returns  to  normal.  Take  another 
starting  record  and  inject  a  second  dose  of  physostigmine. 
You  can  estimate  the  correct  size  of  this  dose  from  the  re- 
sults of  your  first  injection.  When  the  action  of  the  drug 
becomes  marked  on  the  animal  quickly  observe  the  mouth 


riLOCARPINE    AND    TRIMETHYLAMINE 


341 


for  saliva,  tlie  pupils  for  change  in  size,  and  the  respira- 
tory movements  for  difficulty  in  expiration  or  inspiration. 
At  once  inject  one  cubic  centimeter  of  hyoscine  (for  a  dog, 


Fig.  297. — Tracing  showing  the  action  of  pilocarpine  and  triniethylamine  on  the 
bronchioles  and  blood-pressure  in  a  spinal  dog.  Record  made  according  to  the  method 
described  in  Experiment  XXIX. 


one-half  cubic  centimeter  for  a  cat  or  rabbit)  and  observe 
the  effects.  AVhat  conclusions  can  you  draw?  Atropine  or 
liyoscyamine  may  be  substituted  for  the  hyoscine.  How 
does  the  action  of  eserine  compare  with  that  of  piloi»arpine 


342  EXPERIMENTAL    PHARMACOLOGY 

or  muscarine  or  arecoline  f  What  differences  do  you  note  1 
Stimulate  one  vagus  nerve  to  see  if  the  heart  can  be  in- 
hibited. If  so  give  another  dose  of  hyoscine  (or  atropine 
or  hyoscyamine). 

If  the  animal  is  still  in  fair  condition  inject  another  dose 
of  physostigmine  to  see  if  the  respiration,  intestine  and 
circulation  are  atfected  in  the  same  way  as  they  were  be- 
fore the  atropine  was  given.  Do  you  observe  any  fine  mus- 
cular tremors  over  any  parts  of  the  animal?  Were  these 
present  before  the  atropine  was  given  f  Has  the  atropine 
affected  the  tremors  in  any  way!  Explain.  If  you  get  a 
marked  intestinal  reaction  then  inject  one  cubic  centimeter 
of  adrenaline  and  see  what  occurs  in  the  intestinal  record. 
Explain  fully. 

Kill  the  animal  with  a  large  dose  of  eserine.  Which  stops 
first,  the  heart  or  respiration?  Save  the  animal  for  the 
folloAving  experiment. 

EXPERIMENT  XC. 

Adrenaline,  Sodium  Nitrite,  Barium  Chloride.     (Dog,  Cat 
or  Rabbit :    Perfusion  of  Kidney. ) 

(See  preceding  experiment.     Dog's  kidneys  are  much  to 

be  preferred.) 

1.  Observe  carefully  the  arrangement  of  the  apparatus 
shown  in  Fig.  298.  The  water  motor  has  a  wire  rod  at- 
tached eccentrically  by  a  screw  to  the  end  of  the  shaft. 
This  rod  passes  up  to  the  shelf  above  and  ends  in  a  curved 
hook  which  moves  rapidly  up  and  doA\m  and  thus  inter- 
rupts the  flow  of  normal  salt  solution  (or  diluted,  defibrin- 
ated  blood)  from  the  pressure  bottle  (or  bottles)  above. 
This  mechanical  interruption  fairly  closely  approximates 
the  action  of  the  heart  in  producing  a  pulsation  in  the 
atteries  carrying  blood  to  the  various  organs. 

The  apparatus  should  all  be  set  up  and  in  full  working 


PERFUSION    APPARATUS 


343 


condition  with  the  water  bath  heated  to  38  or  39  degrees 
Centigrade  before  the  animal  is  killed.  Also  a  dish  of  warm 
salt  solution,  three  small  cannulas  (for  the  kidney  vessels 
and  ureter),  threads  and  a  rubber  bulb  (1  or  2  oz.)  carry- 
ing a  small  pointed  cannula  should  be  prepared.  The  bulb 
is  used  to  flush  out  the  vessels  of  the  kidney  immediately 


Fig.    298. — Arrangement    of    apparatus    for    perfusion    of    an    excised    organ.      (For    discus- 
sion see   text.) 


after  excision.     This  prevents  clots  from  forming  in  the 
capillaries  and  smaller  vessels  of  the  organ. 

As  soon  as  the  animal  dies  the  abdomen  is  opened  and 
the  left  kidney  is  carefully  excised,  leaving  the  artery,  vein 
and  ureter  as  long  as  possible.  The  kidney  is  immediately 
transferred  to  the  dish  of  warm  salt  solution,  the  rubber 


344  EXPERIMENTAL   PHARMACOLOGY 

bulb  is  drawn  full  of  the  solution  and  the  point  of  the 
cannula  is  inserted  into  the  cut  end  of  the  renal  artery. 
The  cannula  can  be  held  in  temporarily^  while  the  bulb  is 
squeezed  with  a  moderate  but  firm  pressure.  The  blood  is 
soon  flushed  out  of  the  kidney  vessels.  Cannulas  are  then 
quickly  tied  in  the  renal  artery,  vein  and  ureter.  The 
kidney  is  transferred  to  the  small  chamber  shown  in  the 
upper  left  hand  corner  of  Fig.  298.  This  chamber  is  made 
of  a  large,  deep  metal  pill  box  having  a  notch  cut  out  of 
the  upper  side.  Through  this  notch  the  three  cannulas  are 
passed  and  then  the  broad  rubber  band  (which  was  al- 
ready around  the  box)  is  slipped  over  the  notch  while  the 
three  cannulas  in  order  are  passed  through  holes  (air 
tight)  made  in  the  rubber  band.  The  lid  is  then  placed  on 
the  box  and  the  rubber  band  is  slipped  over  the  seam  be- 
tween the  lid  and  the  box  proper  thus  making  the  cham- 
ber air  tight.  The  box  is  then  connected  up  as  shown  in  the 
picture  and  the  stock  solution  is  started  through  the  tubes 
(from  Adiich  all  air  has  been  previously  expelled).  The 
motor  is  started  and  the  pressure  bottle  is  raised  to  a 
height  just  sufficient  to  give  the  maximum  excursion  to 
the  tambour  pointer  at  each  pulsation  of  the  fluid  in  the 
tubes.  The  solution  passes  through  the  kidney  slowly  and 
fresh  (warm)  solution  should  be  run  down  into  the  tubes 
occasionally.  : 

When  all  adjustments  are  made  take  one-half  inch  of 
normal  record  and  then  with  a  hypodermic  syringe  inject 
some  adrenaline  solution  in  the  tube  above  the  artery  as 
illustrated.  A  response  should  be  obtained  at  once  on  the 
drum  if  the  circulation  through  the  kidney  is  good.  Wait 
for  the  kidney  to  expand  again.  Hom^  do  you  explain  these 
results?  As  soon  as  the  contraction  wears  off  (or  a  little 
before)  inject  one  or  two  cubic  centimeters  of  sodium 
nitrite  solution  (one-half  per  cent)  into  the  rubber  tube. 
Note  the  effect  when  this  reaches  the  kidney.  Explain  the 
results  in  full. 


PERFUSION    OF    THE    KIDNEY 


345 


AVlien  a  satisfactory  record  lias  been  o])tained  examine 
the  temperature  of  the  sohition  entering  the  kidney  and  if 
necessary  change  the  pressure  of  the  perfusion  fluid.  (It 
may  be  advisable  to  flush  out  the  organ  by  temporarily 
increasing  the  pressure  considerably.)     When  everything 


/O   B^,cxrrujl4^. 


Fig.  299. — Tracings  made  by  the  use  of  the  apparatus  shown  in  Fig.  298,  showing 
the  action  of  sodium  orthovanadate,  barium  chloride,  and  adrenaline  on  the  volume  of 
an  excised  kidney  from  a  dog.      (For  discussion  see  te.xt.) 


is  again  ready  inject  one  or  two  cubic  centimeters  of 
barium  chloride  solution  (one-half  per  cent).  Wait  for  the 
drug  to  pass  into  the  kidney.  The  circulation  often  be- 
comes slow  in  organs  thus  perfused.  Do  you  get  a  satisfac- 
tory record?    Explain  the  action  of  the  drugs  studied. 


346  EXPERIMENTAL    PHAEMACOLOGY 

The  right  kidney  or  the  spleen  of  the  same  animal  may 
be  used  by  other  members  of  the  class  if  snffiicient  appara- 
tus is  available.  The  motor  and  the  pulsations  in  the  per- 
fusion fluid  may  be  omitted  if  the  apparatus  cannot  be  ob- 
tained. The  interrupted  pressure  is,  however,  much  to  be 
preferred  as  it  is  more  effective  in  keeping  up  the  circula- 
tion through  the  organ  (and  edema  of  the  tissues  may  be 
prevented  or  much  delayed  in  its  appearance).  The  tin 
box  chamber  (oncometer)  may  be  omitted  and  the  rate  of 
perfusion  determined  by  counting  the  drops  of  solution 
leaving  the  vein.  It  is  advisable,  however,  to  get  a  volume 
record  of  the  organ. 

Many  forms  of  perfusion  apparatus  have  been  devised 
and  the  student  may  find  it  necessary  to  use  an  outfit  very 
different  from  that  here  described.  (For  description  of  an 
excellent  perfusion  apparatus,  see  Richards,  A.  N.,  and 
Drinker,  C.  K.:  Journal  of  Pharmacology  and  Experi- 
mental Therapeutics,  1915,  vii,  pp.  467  to  483.) 

EXPERIMENT  XCI. 

Physostigmine,  Atropine,  (Heroine),  Adrenaline.     (Spinal 

Dog  or  Cat:     Bronchioles,  Blood-pressure,  and 

Bladder  Contractions.) 

1.  Arrange  a  spinal  dog  (or  cat  if  dogs  are  not  avail- 
able) for  recording  blood-pressure,  bladder  and  bronchiole 
contractions.  It  is  very  advisable  that  the  lung  records  be 
obtained  by  the  aspiration  method  using  the  apparatus 
shown  in  Fig.  255.  Pith  the  animal  by  destroying  the  brain 
through  a  trephine  opening  (Fig.  260).  (Also  read  Experi- 
ment LXX.)  The  arrangements  for  recording  the  bladder 
contractions  should  be  made  (except  attaching  the  record- 
ing tambour  as  this  would  interfere  with  the  operations) 
before  the  apparatus  used  to  hold  the  chest  open  is  inserted 
and  this  should  be  done  {under  positive  artificial  respira- 
tion) before  the  animal  is  pithed,  whicli  is  the  last  opera- 


ESERINE,    ADRENALINE,    ATROPHSTE  347 

tion  done  before  the  records  are  started.  This  sequence 
of  operative  procedures  is  followed  in  order  to  save  the 
vitality  of  the  animal  as  much  as  possible — a  spinal  animal 
may  not  stand  operations  well.  The  injecting  burettes 
contain  eserine  (one  cubic  centimeter  equals  one  milligram), 
adrenaline  (1:10,000),  and  heroine  (one  cubic  centimeter 
equals  five  milligrams — other  opium  alkaloids,  e.  g.,  co- 
deine, etc.,  may  be  used  instead  of  heroine). 

When  all  apparatus  is  arranged  take  half  an  inch  or 
more  of  normal  record  and  then  inject  one  cubic  centi- 
meter (dog)  of  eserine.  Do  you  get  satisfactory  bladder 
and  lung  records?  A  moderate  dose  of  physostigmine  has 
been  found  to  render  the  endings  of  the  vagi  nerves  in  the 
bronchoconstrictor  muscles  more  irritable  than  normally. 
Allow  the  animal  to  recover  as  much  as  possible  from  the 
drug  and  then  stimulate  each,  or  both,  vagus  nerves  and 
determine  exactly  what  influence  they  possess  over  the  cali- 
ber of  the  bronchioles.  Use  varying  strengths  of  the  Fara- 
dizing  current  and  also  try  varying  lengths  of  duration  of 
stimulation.  It  ma^^  be  further  instructive  to  use  a  series 
of  single  shocks  of  varying  strengths  and  duration  to  bring 
out  any  bronchial  changes.  What  conclusions  can  you 
draw?  (See  Dixon  and  Brodie:  Journal  of  Physiology, 
1903,  xxix,  p.  119;  also  Dixon  and  Ransom,  ibid,  1912.) 

Get  the  animal  into  as  good  condition  as  possible  (give 
adrenaline  if  necessar}^)  and  then  inject  a  second  dose  of 
eserine.  A¥hen  the  effects  come  on  inject  one-half  cubic 
centimeter  of  adrenaline  to  counteract  the  eserine.  Do 
your  records  show  normal  results?  Was  the  dose  of 
eserine  of  the  right  size  ?  ( You  must  learn  to  estimate  the 
dose  to  suit  your  animal  often — the  instructor  can  help 
you  here.) 

AVhen  the  animal  recovers  give  another  dose  of  eserine 
or,  if  a  bronchial  constriction  returns  after  the  adrenaline 
effects  wear  off,  omit  the  eserine  and  then  inject  one  cubic 
centimeter  of  atropine  solution  (one  cubic  centimeter  equals 


348 


EXPERIMENTAL   PHARMACOLOGY 


one  milligram — dog)  and  thus  counteract  the  eserine  ac- 
tion.   How  does  the  bladder  respond  to  these  drugs'? 

If  the  animal  is  still  in  a  suitable  condition  inject  five 
cubic  centimeters  of  heroine  or  other  (phenanthrene)  de- 
rivative of  opium  (dose  for  an  eight  kilo  dog)  and  see  if 


C-ordb'uxxjUxrY^ 


l-iopoo 


Fig.    300. — Tracing  showing  the   action   of  heroine  and   adrenaline   on  the  bronchioles  and 
blood-pressure  in  a  spinal  dog.     Made  by  aspiration  of  the  chest. 

you  can  get  a  bronchoconstriction  or  a  bladder  contrac- 
tion after  atropine.  Counteract  this  Avith  adrenaline  (one 
and  one-half  cubic  centimeters — dog). 

How  does  eserine  affect  the  respiration  in  a  normal  ani- 


PRACTICE    DISSECTIONS  349 

mal?  Does  tlie  action  of  the  drug  on  tlie  bronchioles  in 
^this  experiment  indicate  any  way  in  whicli  the  drug  might 
affect  the  normal  respiration  aside  from  its  direct  action 
on  the  respiratory  center?  Do  you  know  of  any  disease  in 
Avhich  the  lungs  map  he  affected  in  a  manner  similar  to 
that  brought  about  by  eserine?  Do  you  know  of  am' 
remedy  that  might  be  used  to  counteract  each  condition? 
How  might  the  remedy  be  applied?  Stop  the  artificial 
respiration  and  kill  the  animal. 

2.  After  death  (if  you  have  used  a  dog)  shave  the  hair 
off  of  an  area  about  three  inches  long  and  three  inches  wide 
over  the  lower  part  of  the  dorsal  region  of  the  si)ine.  With 
a  scalpel  make  a  small  incision  in  the  skin  al)out  one-half 
inch  to  one  side  of  the  mid-line  of  the  spinal  column.  A 
small  trocar  or  a  long  syringe  needle  (or  even  a  knitting 
needle)  is  noAv  passed  into  the  spinal  canal,  the  needle  or 
trocar  being  directed  inward,  mesially  and  slightly  toward 
the  head.  By  consulting  a  text-book  on  anatomy  the  stu- 
dent can  determine  about  what  relation  the  point  of  inser- 
tion of  the  needle  through  the  skin  should  bear  to  the  lower 
end  of  the  nearest  spinous  process.  See  if  you  can  get 
some  spinal  fluid  to  run  out  of  the  needle  after  it  is  in- 
serted. Two  or  three  punctures  may  be  made  for  practice. 
The  needle  is  then  left  in  position  and  the  tissues  are  dis- 
sected away  around  the  needle  do^^m  to  the  vertebrae  and 
the  position  and  relations  of  the  needle  are  carefully 
studied.  If  you  failed  to  pass  the  needle  into  the  spinal 
canal  what  was  the  cause?  Could  you  now  succeed  in  a 
living  animal?  Sketch  in  your  note  book  the  relations  of 
the  spinous  processes  to  the  openings  into  the  spinal  canal 
and  save  for  reference.  Examine  the  size,  structure  and 
relations  of  the  spinal  cord.  Can  you  isolate  the  posterior 
and  anterior  roots  and  the  spinal  ganglia?  What  are  the 
functions  of  these  structures  ? 


350  EXPEKIMEKXAL   PHARMACOLOGY 

EXPERIMENT  XCII. 
Cocaine.    (Frog:    Central  Nervous  System.) 

1.  Pith  a  frog  (cerebrum  only)  and  wait  a  while  for  the 
animal  to  recover  from  the  shock.  Then  inject  into  the 
anterior  lymph  sac  one  cubic  centimeter  of  cocaine  hydro- 
chloride solution  (one  cubic  centimeter  equals  five  milli- 
grams— one-half  per  cent). 

Observe  the  symptoms  produced  and  save  the  animal  for 
several  hours  (if  it  lives)  to  note  the  later  action  of  the 
drug.  What  conclusions  can  you  draw?  Do  you  find  any 
evidence  of  central  nervous  stimulation?  How  is  the  rate 
of  beat  of  the  lymph  hearts  affected? 

EXPERIMENT  XCIII. 

Cocaine,  Physostigmine.     (Rabbit,  Cat,  Dog,  Pigeon, 
Sparrow,  Chicken,  Rat:    Action  on  Pupil.) 

1.  Into  the  right  eye  of  as  many  of  the  above  animals  as 
you  can  obtain  inject  ten  drops  of  a  one  per  cent  solu- 
tion of  cocaine  hydrochloride.  Open  the  lids,  drop  in  the 
solution  and  try  to  hold  the  eye  open  a  while  to  insure  ab- 
sorption. Wait  ten  minutes  (examine  the  pupils  from  time 
to  time)  and  then  inject  into  the  left  eye  of  each  animal  ten 
drops  of  a  solution  of  eserine  (one  cubic  centimeter  equals 
five  milligrams).  Observe  both  pupils  carefully  from  time 
to  time  and  when  the  actions  of  the  drugs  come  on  try  the 
light  reflex  to  see  if  the  pupil  contracts  Avhen  a  bright  light 
(pocket  flash  light,  lighted  match,  or  bright  light  from  a 
window,  etc.)  is  suddenly  thrown  into  the  eye.  On  what 
does  this  light  reflex  depend?  Explain  in  detail  the  nerv- 
ous paths  involved  in  its  production.  What  differences  do 
you  note  in  the  actions  of  the  two  drugs?  On  what  struc- 
tures does  each  act  and  how?  How  do  these  drugs  affect 
the  intraocular  pressure?    How  is  this  brought  about? 


COCAINE    AND    NOVOCAINE  351 

EXPERIMENT  XCIV. 
Cocaine,  Novocaine.     (Local  Anesthetic  Action.) 

1.  Cut  a  piece  of  filter  paper  one-half  inch  square  and 
saturate  it  Avith  two  per  cent  cocaine  hydrochloride  solu- 
tion. Place  the  filter  paper  on  the  right  side  of  the  upper 
surface  of  the  tongue.  Eepeat  this  for  the  left  side  of  the 
tongue  but  use  a  two  per  cent  novocaine  solution  in  this 
case.  Do  not  sivalloiv  any  of  the  solutions.  Keep  the 
pieces  of  paper  on  the  tongue  for  a  few  minutes  (the  same 
for  each  drug)  and  then  remove  them.  From  time  to  time 
test  the  sensitiveness  of  the  two  spots  on  the  tongue  to 
touch,  pain  (pin  point)  and  to  minimal  induction  currents. 
What  can  you  say  regarding  the  comparative  local  actions 
of  the  cocaine  and  novocaine "?  If  larger  areas  of  the  tongue 
are  covered  by  the  solutions  (to  include  the  taste  organs, 
especially  the  tip  and  edges  of  the  tongue)  then  the  taste 
sensations  for  sweet,  salt,  acid  and  bitter  may  be  tested. 
On  what  parts  of  the  tongue  are  the  taste  organs  to  detect 
each  of  these  sensations  located?  What  conclusions  can 
you  draw  from  the  experiment?  Are  the  sensations  of 
heat  and  cold  affected  or  could  you  determine  this  from 
your  experiment?    Explain  in  detail. 

EXPERIMENT  XCV. 
Cocaine.    (Frog  or  Turtle:    Heart  Tracing.) 

1.  Pith  a  frog  or  turtle  and  test  the  action  of  cocaine  on 
the  heart  and  cardiac  nervous  mechanism  using  a  solution 
containing  two  milligrams  to  one  cubic  centimeter  of  solu- 
tion. Stimulate  the  vagus  before  and  after  the  drug  is 
applied.  Repeat  this  carefully  in  each  case  for  the  crescent 
also.  What  conclusions  can  you  draAv?  Have  you  tested 
other  drugs  having  a  similar  action?     If  so  what  ones? 


352 


EXPERIMENTAL   PHARMACOLOGY 


What  structures  are  involved  in  this  action!  Keep  taking 
records  and  watch  for  a  characteristic  grouping  of  the 
beats  in  fours,  threes,  twos,  etc.  The  drug  is  especially 
liable  to  produce  this  result. 

What  action  would  nicotine  or  lobeline  or  pilocarpine  or 
strychnine  have  on  the  frog  or  turtle  heart  after  cocaine 
had  produced  its  first  effect  on  the  organ!  Is  this  action 
the  same  in  the  mammal !    Explain. 


Fig.  301. — FroR  heart  tracing  showing  the  later  effects  of  cocaine.  Note  the  group- 
ing of  the  beats.  The  earlier  effects  on  the  innervation  of  the  heart  are  not  shown  in 
the  tracing. 


EXPERIMENT  XCVI. 

Cocaine.    (Frog:    Action  on  Muscular  Work.) 

1.  Arrange  your  apjDaratus  as  slioAvn  in  Fig.  224,  Pith 
a  frog  and  ligate  the  right  thigh  tightly  to  stop  the  circu- 
lation in  the  corresponding  gastrocnemius  muscle.  Into 
the  dorsal  lymph  sac  inject  one  cubic  centimeter  of  cocaine 
solution  (one  cubic  centimeter  equals  two  milligrams). 
Arrange  the  frog  with  its  right  gastrocnemius  muscle  at- 
tached to  the  lever  as  shoAvn  in  the  picture.  The  secondary 
wires  are  made  of  very  fine  flexible  copper  and  carry  the 
current  directly  to  the  muscle.     Keep    the    muscle    damp 


COCAINE,    NOVOCAINE,    BAEIUIM,    ADRENALINE  353 

with  normal  salt  solution.     Meanwhile  the  drug  is  being 
carried  to  the  other  gastrocnemius  muscle. 

When  all  is  ready  take  a  normal  fatigue  tracing  on  the 
lower  part  of  the  drum.  Then  lower  the  drum  and  reverse 
the  frog  board  and  corresponding  pieces  of  apparatus  as 
•described  under  caffeine  (Experiment  XL VII,  page  245). 
Ligate  the  left  thigh  and  take  a  fatigue  tracing  from  the 
left  gastrocnemius  muscle  which  has  in  the  meantime  come 
under  the  influence  of  the  cocaine.  How  do  the  two  curves 
compare  as  to  height  of  contractions  and  relative  amount 
of  work  done?  If  there  is  a  difference  to  what  is  it  due? 
Are  any  nervous  structures  involved?  Are  you  sure  the 
rate  of  stimulation  remained  the  same  in  both  tracings? 
AVould  a  slight  variation  in  this  produce  much  effect  on 
the  tracings?  How  does  the  action  of  cocaine  compare 
with  that  of  caffeine  on  muscular  work? 

EXPERIMENT  XCVII. 

Cocaine,  Novocaine,  Barium,  Adrenaline.      (Dog  or  Gat: 

Respiration,  Blood-pressure,  Intraocular  Pressure, 

Local  Vascular  Action  and  Intestinal 

Contractions.) 

1.  Arrange  a  dog  (or  cat)  for  recording  blood-pressure, 
respiration  and  intestinal  contractions,  the  latter  by  means 
of  the  finger  cot,  catheter,  burette  and  tambour  method. 
While  the  abdomen  is  open  pick  out  a  small  area  of  the  in- 
testinal or  mesenteric  wall  where  the  tissues  look  pink 
(many  small  vessels)  and  paint  the  area  mth  cocaine  hy- 
drochloride solution  (two  per  cent).  Also  paint  a  second 
area  with  novocaine  solution  (two  per  cent).  Do  not  ex- 
pose the  viscera  more  than  can  be  helped  but  observe  these 
two  areas  closely  for  several  minutes  to  see  if  any  change 
in  the  appearance  of  the  tissues  occurs.  If  so  how  do  you 
explain  it?    On  a  third  small  area  of  the  intestine  put  one 


354  EXPERIMENTAL   PHARMACOLOGY 

drop  of  barium  chloride  solution  (one  per  cent).  Watch 
this  area  for  a  few  minutes  and  record  your  results.  A 
fourth  area  should  be  treated  with  one  drop  of  adrenaline 
solution  (1:10,000).  Watch  this  spot  a  while  and  compare 
all  the  areas  together.  What  conclusions  and  Avhat  ex- 
planations can  you  offer  ? 

Close  the  abdomen  and  arrange  to  record  the  intra- 
ocular pressure  (see  Fig.  271).  The  injecting  burettes  con- 
tain cocaine  hydrochloride  (one  cubic  centimeter  equals  five 
milligrams)  and  adrenaline  (1:10,000).  On  the  drum  the 
highest  record  should  be  the  intraocular  pressure,  next  be- 
loAv  the  intestinal  record,  then  the  blood-pressure,  respira- 
tion and  base  line  (showing  the  time  intervals). 

Take  a  short  normal  record  and  inject  one-half  cubic 
centimeter  (dog)  of  cocaine  solution.  From  time  to  time 
cautiously  inject  more  cocaine  and  note  the  reactions  of 
the  animal  to  the  drug.  Observe  the  pupils,  palpebral,  fis- 
sure, nictitating  membrane  and  eye  ball  as  a  dose  of  the 
drug  is  injected.  Are  there  any  movements  of  any  of  these 
organs"?  Continue  the  observations  and  stimulate  the  cor- 
responding vagus  nerve.  What  effect  does  this  have  on 
the  palpebral  fissure!  How  do  you  explain  it!  Does  the 
eye  ball  move  ?  If  so  what  muscles  do  this  and  what  is  their 
innervation!    Has  the  intraocular  pressure  been  affected! 

Inject  one-half  cubic  centimeter  of  adrenaline  while  still 
observing  the  eye  and  record  the  results.  Explain  all 
phenomena  observed. 

Continue  to  inject  cocaine  slowly  from  time  to  time  and 
watch  for  irregularities  in  the  respiration. 

(The  animal  should  not  have  been  given  any  morphine. 
It  is  a  very  good  rule  never  to  give  morphine  to  animals 
for  ordinary  experiments  unless  there  is  some  special  rea- 
son for  so  doing.  Ether  is  the  best  anesthetic,  and  a  small 
amount  of  chloretone  may  often  be  given  to  some  advantage 
but. even  this  frequently  causes  serious  cardiac  or  respira- 
tory disturbances.) 


COCAINE    AND    BARIUM  355 

Cocaine  often  causes  Clieyne-Stokes  respiration.  Can 
you  produce  this  in  your  animal!  (AVliat  other  drugs  often 
give  this  form  of  breathing!) 

What  action  has  cocaine  on  the  intraocular  xDressure? 
Does  your  experiment  demonstrate  this !  AVill  the  method 
of  application  of  the  drug  affect  the  result!  If  so  drop 
some  cocaine  solution  into  the  eye  from  Avhich  you  are 
making  your  records.  Does  this  have  aii}^  effect!  AVill  it 
be  absorbed?    Watch  the  pupils. 

What  action  have  small  doses  of  cocaine  on  the  blood- 
pressure  1  Is  this  action  increased  by  larger  doses !  AYhat 
is  the  treatment  for  cocaine  poisoning!  AYoulcl  you  ad- 
vise giving  a  drug  to  lower  the  blood-pressure  in  this  con- 
dition? Would  the  presence  of  an  anesthetic  in  your  animal 
make  any  profound  change  in  the  pharmacological  action 
of  cocaine!  Have  you  used  pure  drugs?  Wliat  are  your 
conclusions  ? 

Wait  a  reasonable  time  for  Cheyne-Stokes  respiration 
to  develop.  Then  empty  out  the  cocaine  solution  and  place 
barium  chloride  solution  (one-half  per  cent)  in  the  burette. 
Adjust  all  writing  pioints  and  take  a  normal  record.  Inject 
four  cubic  centimeters  (dog)  of  barium  solution  (five  cubic 
centimeters  if  the  dog  weighs  ten  kilos  or  more)  and  get  a 
record  showing  the  action  of  the  drug.  How  is  the  intestine 
affected?    The  intraocular  pressure? 

Again  empty  out  the  barium  and  refill  the  burette  with 
novocaine  solution  (one  cubic  centimeter  equals  five  milli- 
grams). Get  the  animal  into  as  good  condition  as  possible 
(give  adrenaline  if  necessary)  and  then  take  a  normal  rec- 
ord. Inject  one-half  cubic  centimeter  of  novocaine  solution 
and  compare  the  action  with  that  of  cocaine.  Inject  a 
larger  dose.  Which  is  more  toxic,  cocaine  or  novocaine? 
(Your  animal  may  not  l)e  nearly  so  sensitive  now  to  small 
doses  of  drugs  as  it  was  in  the  beginning.) 

Empty  out  tlie  novocaine  and  refill  the  burette  with  co- 
caine solution.    Adjust  all  writing  points  and  inject  a  large 


356  EXPERIMENTAL    PHARMACOLOGY 

dose  of  cocaine  to  get  a  death  record.  Are  convulsions  pro- 
duced? AVhat  conclusions  can  you  draw?  AYhich  is  more 
poisonous,  cocaine  or  pilocarpine! 

2,  After  the  animal  dies  dissect  out  the  thoracic  duct 
at  the  root  of  the  neck.  See  if  you  can  do  this  without  pene- 
trating the  chest  cavity.  (See  Figs.  302  and  319.)  Do  you 
find  the  lymphatic  vessel  coming  from  the  head  region? 

3.  Turn  the  body  of  the  animal  over  on  its  side  and  dis- 
sect out  a  section  of  the  back  bone  covering  two  or  three 
vertebrae.  Cut  away  the  laminae  and  remove  the  spinous 
processes  from  two  or  three  vertebrae.  Can  you  isolate  the 
cord?  How  large  is  it?  Can  you  make  out  the  anterior 
and  posterior  nerve  roots?  Locate  a  posterior  nerve  root 
ganglion,  "What  is  the  function  of  this  ganglion  ?  Does  this 
bear  any  relation  to  the  action  of  cocaine?  If  so  what? 
Could  you  pass  a  long  h^^podermic  needle  through  the  skin 
and  tissues  of  the  back  down  into  the  spinal  canal?  Study 
the  anatomy  of  these  structures  carefully  and  try  to  decide 
on  what  technic  you  would  use  in  making  a  spinal  puncture. 

EXPERIMENT  XCVIII. 

Novocaine.     (Dog:     Spinal  Anesthesia.) 

(This  experiment  should  be  performed  only  at  the  discre- 
tion of  the  ins'tructor,  and  then  by  students  who  have 
some  knowledge  of  aseptic  operations.     It  may 
be  done  as  a  demonstration.) 

1.  Sterilize  by  boiling  in  water  for  five  minutes  a  good 
hypodermic  syringe  having  a  large  needle  at  least  two 
inches  long.  Prepare  a  novocaine  solution  (two  per  cent) 
and  sterilize  it  by  boiling  for  a  brief  period  of  time.  Cool 
the  solution  but  see  that  it  does  not  become  contaminated 
with  any  organisms.  (Keep  it  in  a  sterile  test  tube  plugged 
with  sterile  cotton).  Place  on  the  operating  table  a  razor 
(clippers  are  also  desirable),  a  pan  of  strong  soapsuds, 


Fig.  302. — Dissection  showing  the  method  of  exposing  the  lymphatic  ducts  and  con- 
necting cannulas  to  collect  the  lymph  or  chyle.  It  is  very  desirable  to  avoid  entering  the 
apex  of  the  chest  cavity  when  a  cannula  is  placed  in  the  thoracic  duct. 


PRELIMINARY    OrERATIONS 


357 


some  cotton  sponges,  a  bottle  of  alcohol  (95%),  a  bottle  of 
tincture  of  iodine,  a  large  pan  containing  a  liter  of  water 
and  a  bottle  of  liquor  cresolis  compositus.  Two  or  three 
sterile  towels  may  be  used  to  advantage. 

The  operator  washes  and  scrubs  his  hands  thoroughly 
Avith  soap  and  water  and  waits  for  the  assistant  to  prepare 
the  animal. 

When  all  preparations  are  made  a  dog  weighing  prefer- 
ably about  ten  kilos  is  gently  placed  on  its  left  side  on  the 
operating  board  and  tied  down.     Do  not  excite  or  scare 


Fig.  303.— Metallic  muzzle  (made  of  sheet  brass)  for  administering  an  anesthetic  to 
a  dog  by  the  closed  method.  A  heavy,  perforated  rubber  membrane  is  tied  (with  wire; 
over  the  rear  end  of  the  muzzle.  The  animal's  nose  and  mouth  are  thrust  through  the 
opening  in   the   rubber   membrane. 

the  animal.  Nitrous  oxide  and  oxygen  are  then  admin- 
istered to  the  animal  until  it  becomes  unconscious.  This 
is  best  done  with  an  apparatus  like  those  sho^Am  in  Figs. 
116,  118,  and  172.  It  usually  requires  at  least  ten  minutes 
to  get  a  dog  fairly  deeply  anesthetized  A\ath  nitrous  oxide 
(and  oxygen).  It  is  assumed  that  the  students  have  previ- 
ously had  some  experience  in  giving  nitrous  oxide  to  dogs 
in  the  experiments  in  the  earlier  part  of  the  course.  The 
animal  has  the  metal  muzzle  (Fig.  303)  placed  over  its  nose 


358  EXPERIMEISTTAL   PHARMACOLOGY 

and  mouth  and  the  muzzle  is  connected  to  the  apparatus 
directly,  the  muzzle  flange  being  slipped  over  the  spout  on 
the  pan.  The  connection  is  made  air  tight  by  a  broad  rub- 
ber band.  The  pan  is  filled  with  pure  NoO  and  the  anes- 
thesia is  brought  on  as  rapidly  as  possible.  Ox^^gen  is 
added  in  small  quantities  as  needed.  (The  usual  mistake 
is  in  giving  too  much  oxygen.)    Watch  the  pulse  b}^  keeping 


Fig.    304. — Mew    of    the    reverse    side    of    the    metallic    muzzle    shown    in    Fig.    303.      The 
flange  which  is  not  being  used  is  closed  by   a  rubber  stopper. 

one  finger  over  the  left  femoral  artery  all  the  time.  The 
heart  will  become  slow  but  a  little  fresh  oxygen  will  ac- 
celerate it  (this  sometimes  acts  almost  like  giving  adrena- 
line so  far  as  one  can  tell  by  feeling  the  pulse). 

As  soon  as  the  animal  becomes  quiet  an  assistant  scrubs 
an  area  about  four  inches  in  diameter  over  the  lumbar  por- 
tion of  the  spinal  column  vigorously  with  soap  and  water. 
The  hair  over  the  area  is  then  clipped  and  the  skin  is  shaved 
closely.  The  area  is  washed  thoroughly  with  alcohol  and 
allowed  to  dry.  Tincture  of  iodine  is  then  painted  (with  a 
small  cotton  sponge)  thoroughl}^  over  the  area. 

An  assistant  now  j)ours  about  half  an  ounce  of  the  com- 
pound cresol  solution  (lysol  may  be  used)  into  the  water  in 
the  large  pan.  The  operator  mixes  the  cresol  (or  lysol)  in 
the  vrater  and  thoroughly  scrubs  his  hands  in  the  solution. 


INTRASPINAL    ANESTHESIA  359 

Some  alcohol  may  now  be  poured  on  the  operator's  hands 
(he  should  not  wipe  this  oft').  The  oi:)erator  now  takes  up 
the  syringe  which  had  been  laid  on  a  sterile  towel  to  cool. 
Great  care  mnst  be  used  to  see  that  neither  the  syringe  nor 
the  operator's  hands  touch  anything  which  has  not  been 
sterilized.  The  operator  now  draws  the  barrel  of  the  syringe 
full  of  the  novocaine  solution.  The  syringe  point  is  then 
detached  from  the  barrel  of  the  syringe  which  is  laid  aside 
on  the  sterile  towel  (or  in  a  sterile  pan — a  metal  pan  can  be 
quickly  sterilized  by  pouring  a  few  cubic  centimeters  of 
95%  alcohol  into  it,  fiomng  the  alcohol  over  all  the  inner 
surface  of  the  pan  and  then  setting  fire  to  the  alcohol. 
When  the  pan  cools  it  is  ready  for  use.) 

The  operator  selects  a  point  of  entrance  for  the  needle 
about  three-eighths  of  an  inch  to  the  right  side  of  the  mid- 
line and  a  little  caudal  ward  from  the  tip  of  the  spinous 
process  of  one  of  the  anterior  lumbar  vertebrae.  The  needle 
is  inserted  by  directing  it  slightly  toward  the  mid-line  and 
a  little  in  the  direction  of  the  head.  If  the  needle  hits  the 
spinal  canal  correctly  some  spinal  fluid  may  escape.  (It  is 
very  desirable  to  have  a  needle  which  carries  a  plunger  in- 
side, i.  e.,  a  trocar  and  cannula  to  fit  the  h^^podermic  syringe. 
In  this  case  the  plunger  is  withdrawn  after  the  needle  is  in- 
serted and  fluid  can  flow  out  more  readily.)  When  the 
needle  is  inserted  into  the  canal  the  barrel  of  the  syringe  is 
picked  up,  any  air  which  it  may  contain  is  expelled  after 
which  the  barrel  is  attached  to  the  needle  (which  has  been 
left  in  place)  and  one  cubic  centimeter  of  novocaine  solu- 
tion is  injected  into  the  spinal  canal.  The  needle  is  then 
withdrawn  and  the  opening  may  be  covered  with  a  drop  of 
collodion. 

The  animal  is  quickly  untied  and  the  muzzle  is  removed. 
If  the  gas  has  been  given  properly  and  the  dog  was  a  suit- 
able subject  for  this  form  of  anesthesia  {some  dogs  cannot 
he  anesthetized  irell  at  all  if  ill)  f/as)  recovery  from  the  XoO 
should  occur  in  a  few  minutes.     Place  the  animal  on  the 


360  EXPERIMENTAL    PHARMACOLOGY 

floor  ill  a  quiet  place  and  watch  it  carefully.  Is  there  any 
disturbance  of  motion  in  the  hind  legs  I  If  so  does  this  ex- 
tend to  the  fore  legs  also?  After  a  few  minutes  test  the 
hind  limbs  for  sensation  and  see  if  the  animal  feels  pain  on 
being  pricked  gently  with  a  pin  or  stimulated  with  an  in- 
duced current,  etc.  Are  there  respiratory  or  cardiac  dis- 
turbances? Was  the  dose  too  large  or  too  small  I  Is  there 
any  disturbance  of  heat  or  cold  sensations  in  the  hind 
limbs  1 

Keep  the  animal  under  a  close  observation  for  several 
days,  watching  particularly  for  signs  of  infection  or  men- 
ingitis. How  long  does  it  take  for  the  effects  of  the  drug 
to  pass  off?  If  signs  of  infection  appear  the  animal  must 
at  once  he  chloroformed. 

On  what  structures  within  the  spinal  canal  does  the  drug 
act  to  produce  the  symptoms  observed  ? 

Could  you  demonstrate  this  action  on  a  mixed  (sensory 
and  motor)  nerve  in  any  of  the  peripheral  nerves  of  the 
body?  If  so  how  would  you  do  the  experiment?  AYould  the 
vagus  be  a  suitable  nerve? 

EXPERIMENT  XCIX. 
Ergot.     (Rooster:    Action  on  Comb.) 

1.  A  Avliite  Leghorn  rooster  should  be  selected  for  the 
experiment.  The  rooster  should  not  be  fed  for  twenty-four 
hours  before  the  experiment  is  performed. 

Examine  the  color,  temperature  and  general  appearance 
of  the  comb  and  wattles.  Then  with  a  hypodermic  syringe 
inject  deep  into  the  breast  muscles  five  cubic  centimeters 
of  a  first-class-  preparation  of  fluid  extract  of  ergot 
( Squibb 's  is  usually  satisfactory).  (The  drug  may  also  be 
given  into  the  crop  with  a  soft  rubber  catheter.) 

Place  the  animal  in  a  quiet  place  and  observe  it  carefully 
from  time  to  time  for  at  least  one  or  two  hours.     Do  you 


ACTION    OF    EKGOT  ovjl 

note  any  change  in  tlie  appearance  of  the  comb  and  watth;'S  ? 
If  so  at  what  time  after  the  injection  is  the  change  at  its 
maxinimnf  If  yon  had  a  standardized  preparation  and  a 
ncn-standardized  preparation  of  the  flnid  extract  of  ergot 
could  you  compare  the  relative  strengths  of  these  two  solu- 
tions by  their  relative  actions  in  the  same  sized  doses  on 
roosters  of  approximately  the  same  size,  age,  and  sensitiv- 
ity to  the  drug !  This  is  one  of  the  methods  sometimes  used 
to  standardize  ergot.  (For  literature,  see  Edmunds  and 
Hale:  Bulletin  No.  76,  Hygiene  Laboratory,  U.  S.  Public 
Health  and  Marine  Hospital  Service;  also  Pittenger:  Bio- 
chemic  Drug  Assay  Methods,  P.  Blaldston's  Son  &  Co.) 

EXPERIMENT  C. 
Erg-ot.     (Frog:    Capillary  Circulation.) 

1.  Take  a  thin  board  about  four  inches  wide  by  seven  or 
eight  long  (a  cigar  box  lid  is  very  satisfactory)  and  cut  a 
hole  about  one  inch  in  diameter  in  one  end  and  near  the  side 
as  shown  in  Fig.  305.  Fasten  a  frog,  ventral  side  down- 
Avard,  on  the  board  as  indicated  \yiih  strings  (except  the 
right  hind  leg).  Draw  the  web  of  the  right  hind  leg  over 
the  hole  in  the  board  and  fasten  (^^ith  U\me  strings)  the 
toes  in  an  extended  position  to  spread  the  web  out  well. 
Place  the  board  on  the  stage  of  a  microscope  and  examine 
the  capillary  circulation  in  the  web.  Note  carefully  the  size 
and  appearance  of  the  capillaries  and  the  rate  of  foir  of 
the  corpuscles.  Make  a  sketch  to  show  Avhat  you  see,  ob- 
serving especially  the  size  of  some  of  the  vessels  which  you 
see  where  they  bear  a  certain  relation  to  the  pigment  spots. 
If  the  diameter  of  the  arteriole  changes  can  you  detect  the 
variation  hy  reference  to  the  pigment  s^Dots  I 

Under  the  skin  of  the  back  inject  one-half  cubic  centi- 
meter of  fluid  extract  of  ergot  and  watch  the  circulation 
carefully  from  time  to  time  as  the  drug  is  absorbed.  Do 
you  get  any  change  in  caliber?    If  so  how  do  you  explain 


362 


experimek:tal  pharmacology 


it?  (Greene).  Does  the  alcohol  in  the  drug  have  anything 
to  do  with  your  findings?  Is  the  rate  of  movement  of  the 
corpuscles  affected? 

Meanwhile  observations  may  be  made  on  the  retinal  ves- 


Toes  fastened 
with  strings 


Fig.    305. — Arrangement    of   apparatus    for    observing   the    capillary    circulation   in    the    web 

of   a   frog's   hind   limlj. 

sels  with  the  ophthalmoscope  (room  darkened).  Do  you 
note  any  change  here ?  What  conclusions  can  you  draw?  A 
second  frog  may  be  injected  with  alcohol  (same  strength  as 
that  in  the  extract)  and  the  results  compared  with  those 
from  the  ergot  frog. 


TYRAMINE,    ERGAMIJSTE,    ERGOTOXIXE  363 

EXPERIMENT  CI. 
Tyramine.     (Frog:    Capillary  Circulation.) 

1.  Repeat  the  above  experiment  on  a  fresh  frog  using  a 
solution  of  tyramine  (parahydroxyphenylethylamine — Bur- 
roughs A¥ellcome  and  Co.,  New  York).  The  solution  may 
be  made  up  from  the  hypodermic  tablets  (one  cubic  centi- 
meter equals  four  milligrams).  Inject  one  cubic  centimeter. 
Repeat  the  observations  and  state  your  conclusions.  AVhat 
are  the  active  principles  found  in  ergot!  (See  Dale,  Barger, 
Laidlaw,  Dixon:  Journal  of  Ph^-siology,  xxxiv,  xxxix,  xli, 
xliii;  Biochemical  Journal,  ii;  Archiv  fiir  experimentelle 
Pathologie  und  Pharmakologie,  Ixi.) 

EXPERIMENT  CII. 

Ergamine.    (Turtle:    Lung  Tracing.) 

1.  Prepare  a  turtle  to  record  a  lung  tracing.  Take  a  nor- 
mal and  inject  one  cubic  centimeter  of  ergamine  solution 
(five  cubic  centimeters  equal  one  milligram)  into  the  heart. 
Record  the  results  and  discuss  your  conclusions  in  full. 
Give  different  sized  doses  if  necessary  to  get  good  results. 

EXPERIMENT  CIII. 

Ergotoxine,  Ergamine,  Adrenaline,  Barium.     (Dog  or  Cat: 

Blood-pressure,  Respiration,  Uterine  Contractions — 

Barbour's  Method.) 

1.  Arrange  a  dog  (or  cat)  for  taking  blood-pressure  and 
respiration  tracings.  Open  the  abdomen  and  gently  move 
the  intestines  upward  toward  the  diaphragm.  Expose  the 
uterine  horns  and  ovaries.  With  great  care  dissect  the 
ovaries  loose  from  the  underlying  tissues  and  then  gently 
raise  the  two  horns  upAvard  and  slowly  dissect  loose  the 


364 


EXPERIMENTAL   PHARMACOLOGY 


vessels  and  tissues  holding  the  uterus  down.  Use  the  great- 
est care  not  to  injure  the  blood-vessels  or  nerves  going  to 
the  uterine  horns  both  of  which  are  brought  together  at  the 
upper  ends.  These  ends  are  now  tied  with  a  thread  whicli 
is  passed  through  a  metal  tube  as  shown  in  Fig.  306. 


Fig.  306. — Arrangement  of  animal  and  apparatus  for  recording  uterine  contractions 
according  to  the  method  of  Barbour.  (See  Jour,  of  Tharm.  and  Exper.  Therapeutics, 
1915,  vii,  p.  547.) 

The  tube  is  lowered  into  the  abdomen  over  (around)  the 
uterus,  the  two  horns  of  wiiich  are  pulled  up  as  illustrated. 
The  tube  is  placed  do^\ai  in  position  (be  sure  the  bladder — 
which  should  be  empty — is  not  caught  inside  the  lower  end 
of  the  tube)  and  the  abdomen  is  closed  air  tight  with  hemo- 


RECORDING    UTERINE    CONTRACTIOjSTS 


365 


stats.  The  tube  is  held  in  a  large  clamp  attached  to  a  stand. 
The  thread  is  brought  upward  over  a  very  sensitive  pulley 
(one  with  jeweled  bearings  is  preferred)  about  one  inch  in 
diameter  and  thence  is  directed  toward  the  drum  where  it 
passes  o^'er  another  pulley  and  is  then  connected  to  a  frog 
heart  lever  which  records  the  contractions. 


Fig. 


30". — Tracing   showing   the    action    of   barium   chloride    on    the    uterus,   blood-pressure 
and    respiration   in   a   dog.      Tracing   obtained   by   Barbour's    method. 


The  injecting  l)urettes  contain  adrenaline,  ergamine  and 
ergotoxine  phosphate.  Ergotoxme  pliosphate  is  sold  by 
Burroughs,  AVellcome  &  Co.,  New  York  and  London.  It  is  a 
fine  brown  powder  (one  gram  vials,  $7.00  or  $8.00  each)  in- 


366  EXPERIMENTAL    PHARMACOLOGY 

soluble  in  water  and  is  dissolved  as  follows :  Weigh  out  the 
required  amount,  perhaps  one  hundred  milligrams,  and 
place  it  in  a  dry  beaker.  Over  the  powder  pour  three  or 
four  drops  of  ten  per  cent  sodium  hydrate  solution  and  stir 
the  powder  into  the  solution.  Two  or  three  drops  of  water 
are  slowly  added  from  time  to  time  as  the  drug  goes  into 
solution.  When  all  the  powder  is  dissolved  Avater  is  added 
to  bring  the  solution  to  the  desired  strength  (one  cubic 
centimeter  equals  five  milligrams).  Since  the  drug  is  ex- 
pensive it  is  sometimes  advisable  to  make  up  only  a  small 
amount  and  inject  each  dose  directly  into  a  vein  (femoral  or 
external  jugular)  with  a  hypodermic  syringe. 

The  metal  tube  in  the  abdomen  is  filled  high  enough  to 
cover  the  uterine  horns  with  petrolatum  liquidum  (liquid 
parafhn).  This  protects  the  uterus  against  cooling  or  dry- 
ing. 

When  all  adjustments  are  made  arrange  the  writing- 
points  on  the  drum  (slow  speed)  Avith  the  uterine  record  at 
the  top.  Take  a  normal  and  determine  what  weight  (ten- 
sion) the  uterus  can  best  counteract.  When  all  is  ready 
watch  the  pupils  closely  and  inject  two  cubic  centimeters  of 
ergotoxine  (dog — 7  or  8  kilos)  and  record  the  results.  How 
does  the  record  compare  with  one  made  by  adrenaline? 
How  long  does  the  change  in  blood-pressure  last?  AVait  till 
the  drug  has  shown  its  action  (perhaps  four  to  six  inches  on 
a  slow  drum).  Did  the  uterus  contract?  How  do  you  ex- 
plain this?  There  is  great  variation  in  this  respect  in  dif- 
ferent animals  and  species.  Inject  one-half  cubic  centi- 
meter of  adrenaline.  How  does  this  drug  act  now  as  com- 
pared with  the  result  in  a  normal  animal  ?  Do  you  note  any 
changes?  (The  size  of  the  close  of  ergotoxine  is  of  im- 
portance here — more  can  be  injected  later.) 

Get  the  animal  into  as  good  condition  as  possible  and  take 
a  normal.  Watch  the  pupils  and  inject  two  cubic  centi- 
meters of  ergamine  (histamine — Burrouglis,  Wellcome  & 
Co. — put  up  in  hypodermic  tablets — make  solution  ten  cubic 


ERGAMINE    AND    ADRENALINE 


obi 


centimeters  to  one  milligram)  and  record  the  results.  Do 
you  get  a  contraction  of  the  uterus?.  How  is  the  blood-pres- 
sure affected"?  The  respiration?  If  the  animal  is  about  to 
die  inject  one  cubic  centimeter  of  adrenaline  and  see  how 
this  counteracts  the  respiratory  and  vascular  actions  of  the 
ergamine.  Does  this  affect  the  uterus  ?  In  what  ways  may 
the  adrenaline  act  to  change  the  respiration  of  this  animal? 
Wait  a  while  and  let  the  animal  recover   (if  necessary). 


Fig.  308. — Tracing  showing  the  action  of  ergamine  (histamine)  and  adrenaline  on 
the  respiration  (stethograph  drum  around  chest)  and  blood-pressure  in  a  dog.  Ergamine 
causes  profound  tetanic  contraction  of  the  bronchioles  and  shrinkage  of  the  volume  of 
the  lungs.  This  makes  more  difficult  (and  hence  decreases)  the  normal  respiratoi-y 
movements.  This  action  may  be  accompanied  by  more  or  less  depression  of  the  respira- 
tory center  by  the  drug  but  the  peripheral  action  is  so  powerful  that  it  must  be  greatly 
concerned  in  the  decrease  of  the  respiratory  movements.  Adrenaline  (which  dilates  the 
bronchioles)  promptly  relieves  the  respiratory  embarrassment.  Down  stroke  is  inspira- 
tion. Does  the  animal  have  difficulty  in  inspiration  or  expiration?  How  does  the 
adrenaline   affect   this?      How   is   the   intrathoracic    pressure   aiTected? 


368 


EXPEEIMENTAL    PHARMACOLOGY 


Were  the  records  from  the  ergamine  satisfactory?  If  so  no 
more  of  the  drug  need  be  given  at  present,  but  if  the  records 
were  poor  (dose  too  small  or  too  large)  a  second  injection 


Fig.  309. — Tracing  showing  ths  action  of  ergamine  (histamine)  on  the  rate  ot  oxygen 
consumption,  blf^od-rressure  and  resoiraUon  in  a  dog.  The  marked  fall  in  blood-pressure 
is  not  accompanied   by  a  correspondingly  great  change  in   oxygen   consumption. 


may  be  given,  the  dose  being  estimated  from  the  previous 
results.  Let  the  animal  recover  (giving  one-half  cubic 
centimeter  of  adrenaline  if  necessary). 


EllGAMlNE,    ADRENALINE,    TYRAMINE  369 

Now  inject  cautiously  in  small  repeated  doses  several 
cubic  centimeters  of  ergotoxine.  How  is  the  blood-pressure 
affected  f  Examine  the  pupils  from  time  to  time  and  note 
any  change.  Stimulate  one  vagus  nerve  and  observe  the 
effect  on  the  corresponding  pupil  and  the  heart.  Does  the 
blood-pressure  fall  to  a  low  level  and  remain  there?  Does 
the  ergotoxine  now  fail  to  raise  the  blood-pressure  (in  the 
same  sized  dose  as  that  first  given) !  Get  the  animal  into  as 
good  condition  as  possible  and  inject  one  cubic  centimeter 
of  adrenaline.  Do  you  get  a  marked  rise  in  blood-pressure  1 
Does  the  uterus  react?  Was  the  dose  large  enough?  Ex- 
plain your  results  in  detail.  What  structures  have  been  in- 
volved and  how  are  they  affected?  Do  your  results  cor- 
respond with  those  described  in  the  literature? 

Empty  out  the  ergamine,  fill  the  burette  with  one-half  per 
cent  barium  chloride  and  inject  five  cubic  centimeters  (dog). 
Do  you  get  a  rise  in  blood-pressure  or  a  contraction  of  the 
uterus?  On  what  structures  does  the  barium  act?  Have 
these  been  affected  by  the  other  drugs  ? 

Kill  the  animal  with,  barium.  After  death  dissect  out  the 
thoracic  duct  in  the  neck  and  place  a  thread  around  it.  (See 
Figs.  302  and  319.)  Also  dissect  out  the  left  j^ulmonary 
artery  (Figs.  274,  275,  276,  and  277). 

EXPERIMENT  CIV. 

Ergamine,  Adrenaline,  Tyramine,    (Codeine  or  Heroine). 

(Dog:    Blood-pressure,  Pulmonary  Blood-pressure, 

Respiration.) 

1.  The  dog  should  weigh  at  least  eight  or  ten  kilos.  It  is 
advisable  to  give  a  small  dose  of  chloretone.  Arrange  for 
recording  blood-pressure  and  set  up  the  two  manometers 
(one  for  the  pulmonary  pressure)  as  shown  in  Fig.  273. 
Read  over  the  directions  for  Experiment  LXXVII,  p.  310, 
carefully,  and  prepare  to  follow  out  the  technic  given  there 


370 


EXPEKIMENTAL   PHARMACOLOGY 


RECORDING   PULMOXARY    BLOOD-PRESftURE  371 

for  recording  pulmonary  blood-pressiire.  In  this  present 
experiment,  hoAvever,  arrange  first  to  take  a  record  of  the 
action  of  tyramine.  Kecord  the  blood-pressure  (carotid) 
and  the  respiration  (stethograph). 

Tyramine  is  sold  in  the  form  of  hypodermic  tablets  (0.020 
gram — Vs  gram  each)  by  Burroughs,  Wellcome  &  Co.  Make 
a  solution  containing  five  milligrams  to  one  cubic  centi- 
meter. (It  may  be  advisable  to  inject  this  with  a  hypo- 
dermic syringe  into  the  external  jugular  or  femoral  vein 
to  avoid  using  more  drug  than. is  necessary.) 

Adjust  the  writing  points  on  the  drum,  take  a  normal 
record  and  inject  one  cubic  centimeter.  You  should  get  a 
rise  in  pressure  Avhich  persists  for  some  time.  Wait  for  the 
effects  of  this  to  wear  off  and  save  your  animal  as  it  will 
need  all  the  vitality  it  has  for  the  next  part  of  the  exx)eri- 
ment.  On  what  structures  does  tyramine  act?  To  what 
other  drug  is  it  most  similar  in  action?  How  does  it  differ 
from  ergotoxine? 

Remove  the  stethograph  and  insert  a  cannula  (see  Fig. 
279)  into  the  left  pulmonary  artery.  The  injecting  burettes 
(femoral  veins)  contain  ergamine  (ten  cubic  centimeters 
equal  one  milligram,  see  Experiment  CII)  and  adrenaline 
(1:10,000).  Be  sure  the  artificial  respiration  is  being  car- 
ried out  satisfactorily  and  that  the  animal  does  not  get  too 
much  (nor  too  little)  ether. 

Adjust  the  writing  points,  take  a  normal  and  inject  one- 
half  cubic  centimeter  of  adrenaline.  Is  your  adrenaline 
preparation  satisfactory?  (Many  samples  are  spoiled  be- 
fore the  bottles  are  opened  and  an  exposed  solution  rapidly 
deteriorates.)     (See  Fig.  311.) 

When  the  records  return  to  normal  ivafcli  the  Jungs 
closely  and  inject  tAvo  cubic  centimeters  of  ergamin^^  solu- 
tion (or  less  if  the  animal  is  small)  and  record  the  results. 
How  is  the  carotid  pressure  affected?  Did  you  see  any 
change  in  the  relative  extent  of  expansion  and  contraction 
of  the  lungs  Avith  each  inflation  from  the  respiration  ma- 


372 


EXPERIMENTAL   PHARMACOLOGY 


ERGAMINE,    HORDENINE,    ATROPINE  373 

chine?  If  your  drug  was  pure  and  the  dose  suited  to  the 
dog  you  should  see  the  lung  changes.  To  what  do  these  cor- 
respond? Was  the  pulmonary  blood-pressure  affected! 
How  was  this  brought  about?  What  structures  were  in- 
volved and  how  Avere  they  affected?  (See  Cloetta:  Archiv 
fiir  experimentelle  Pathologie  und  Pharmakologie,  1914). 
AVhat  relation  does  a  dilatation  of  the  bronchioles  bear  to 
the  pulmonary  pressure  ?  What  relation  does  a  contraction 
of  the  bronchioles  bear  to  the  pulmonary  pressure? 

If  the  animal  is  still  in  a  fair  condition  give  it  a  dose  of 
adrenaline  and  change  the  ergamine  solution  for  one  of 
codeine  or  heroine  (one  cubic  centimeter  equals  five  milli- 
grams). You  must  w^ork  ciuickly  for  the  animal  may  die  at 
any  time.  Inject  five  cubic  centimeters  of  the  codeine  (or 
heroine)  solution  [ivatch  the  lungs)  and  compare  the  pul- 
monary reaction  here  with  that  under  ergamine. 

Kill  the  dog  with  one  of  your  solutions.  Make  a  diagram 
showing  the  complete  innervation  of  the  lungs. 

EXPERIMENT  CV. 

Ergamine,  Adrenaline  (or  Hordenine),  Atropine.     (Spinal 
Dog,  or  Cat:     Bronchioles.) 

(Bladder  contractions  may  also  be  recorded  if  desired.) 

1.  A  number  of  methods  have  previously  been  described 
for  recording  bronchial  contractions.  AVith  positive  arti- 
ficial respiration  in  a  spinal  dog  a  perforated  brass  tube  can 
be  passed  through  the  chest,  or  by  use  of  the  lung  shield 
(Fig.  200)  a  bent  glass  tube  can  be  inserted  through  the 
right  chest  wall  to  record  changes  in  the  right  lung  only,  or 
by  use  of  the  special  forms  of  apparatus  shoA\m  in  Figs. 
255  and  256  the  entire  chest  cavity  can  be  used  as  a  ple- 
thysmogrrph  frcm  which  a  tube  is  led  off  to  the  large  howled 
recording  tambour  (Figs.  14  and  372).  With  the  negative 
pressure  method  of  carrying  out  artificial  respiration  by 
means  of  aspirating  the  chest  cavity  after  one  or  the  other 


374  EXPERIMENTAL   PHARMACOLOGY 

of  tlie  special  pieces  of  apparatus  shown  in  Figs.  255  and 
256  have  been  inserted  into  the  chest  the  best  results  can 
be  obtained.  The  writer  recommends  that  all  laboratories 
which  can  afford  it  build  some  such  form  of  universal  arti- 
ficial respiration  machine  as  those  shown  in  Figs.  360  and 
364  or  that  where  both  positive  and  negative  air  pressure  is 
already  available  to  the  laboratory  a  universal  valve  like 
those  shown  in  Figs.  365  and  366  be  obtained.  Cats  can  be 
used  very  well  for  lung  tracings  by  the  aspiration  method, 
in  fact  in  some  respects  they  are  better  than  dogs,  but  the 
larger  size  and  greater  vitality  of  dogs  make  them  prefer- 
able as  a  rule. 

By  one  of  the  methods  previously  given  arrange  to  take 
a  record  of  the  bronchial  muscle  changes  and  to  record  the 
right  carotid  blood-pressure.  The  arrangements  for  re- 
cording blood-pressure  should  be  completed  first.  The  in- 
jecting cannulas  are  next  inserted  and  the  burettes  are  filled 
with  ergamine  solution  (ten  cubic  centimeters  equal  one 
milligram)  and  with  adrenaline  (1:10,000)  or  hordenine 
(one  cubic  centimeter  equals  ten  milligrams — this  can  be 
bought  of  Burroughs,  Wellcome  &  Co. — 1  gram  $1.80,  solu- 
ble in  water  on  heating). 

The  chest  is  now  opened  (if  this  method  is  to  be  used) 
and  the  apparatus  is  inserted  (using  positive  artificial  res- 
piration). Two  courses  are  now  open  as  f oHom'^s  : — 1st,  If 
positive  artificial  respiration  (a  hand  bellows  may  be  used 
if  nothing  else  is  obtainable)  must  be  used  throughout  the 
experiment  the  tambour  tube  is  noAV  connected  to  the  ap- 
paratus in  the  chest  and  a  record  about  three  inches  in  am- 
plitude on  the  drum  should  be  arranged  for  by  making  the 
proper  magnification  for  the  writing  point,  regulation  of 
the  expansion  of  the  lungs,  etc.  If  one  has  a  well-fitting 
piece  of  apparatus  in  the  chest  he  need  not  necessarily  pith 
the  dog  by  this  method  but  it  is  usually  advisable  to  do  so 
to  keep  the  animal  quiet  and  to  avoid  the  anesthetic.  2nd, 
If  negative  artificial  respiration  can  be  used,  then  after  the 


BRONCHIAL    TRACINGS  6(.} 

apparatus  is  fully  adjusted  in  the  chest  tlie  animal  is  pithed 
and  the  recording  tambour  is  attached  to  the  straight  end 
of  the  tracheal  cannula,  the  side  tube  of  the  cannula  having 
a  short  rubber  tube  with  an  adjusting  screw  clamp  (Hof- 
mann's)  attached  to  it.  The  ether  is  removed  as  a  spinal 
animal  needs  no  further  anesthetic  at  all.  Pithing  is  car- 
ried out  by  trephining  the  skull  and  destroying  the  brain 
and  upper  part  of  the  cord  as  described  and  illustrated  in 
Experiment  LXX,  page  292.  (Experiment  LXX  should  be 
read  over  before  this  one  is  started  as  the  technic  is  the 
same  in  each  and  the  figures  given  there  will  be  needed  for 
the  present  experiment.) 

After  the  dog  is  pithed  the  head  is  returned  to  its  former 
position  and  the  shift  from  positive  to  negative  artificial 
respiration  is  made.  The  recording  tambour  is  attached 
(by  a  glass  reducer)  to  the  short  piece  of  three-eighths  ii>ch 
rubber  tubing  on  the  straight  end  of  the  tracheal  cannula 
and  the  large  hoivled  tambour  is  adjusted  to  give  a  record 
of  about  three  inches  in  amplitude  placed  just  above  the 
blood-pressure  (which  should  be  about  three-fourths  to  one 
inch  above  the  base  line).  Inspiration  corresponds  to  the 
downstroke  of  the  tambour. 

When  all  adjustments  are  made  take  three-fourths  or  one 
inch  of  normal  record  (be  sure  everything  is  working  all 
right — otherwise  readjust  the  apparatus).  Now  with  care 
stimulate  each  or  both  vagus  nerves  and  determine  exactly 
what  influence  these  have  on  the  bronchioles.  What  con- 
clusions can  you  drawf  Explain  in  detail.  Take  another 
normal  and  then  inject  one  cubic  centimeter  {dog)  of  er- 
gamine  solution.  You  should  get  an  immediate  response. 
If  you  do  not  the  dose  may  have  been  too  small  (possibly  de- 
teriorated drug — but  this  is  rare)  and  you  can  let  the  animal 
recover  and  then  give  a  larger  dose.  The  right  sized  dose 
will  give  a  profound  bronchoconstriction.  "\^^len  this  is  at 
its  maximum  inject  one-half  cubic  centimeter  of  adrenaline 
(or  four  cubic  centimeters  of  hordenine  solution)  and  note 


376 


EXPERIMENTAL   PHARMACOLOGY 


the  results.    (See  Fig.  312.)    What  structures  are  involved 
and  how  are  they  affected  1 

As  soon  as  you  get  one  good  tracing  from  the  ergamine 
then  empty  it  out  and  fill  the  burette  (or  connect  a  third 


wmmmm\\\ 


fljb.CcJu^Xd 


11  1 1  I  M  1 1 1  I  I  1 1 1  M  I  I  H  M  I  1 1 1  I  1 1 1  f  1 1 1 1  Ml  1 1  1 1  III  llllllJIJli 


Fig.  312. — Tracing  showing  the  action  of  ergamine   (histamine,  jS-iminazolylethylamine) 
and   hordenine   on   the   bronchioles    and  blood-pressure   in   a   spinal   dog.      Curara   had   been 


burette  to  an  external  jugular  vein)  with  atropine  solution 
(one  cubic  centimeter  equals  one  milligram).  Start  the 
drum  and  inject  one  cubic  centimeter  of  the  atropine.  Then 
stimulate  the  vagus  nerves  and  see  if  the  bronchioles  or 


BRONCHIOLE    TRACINGS 


6i  ( 


378 


EXPERIMENTAL   PHARMACOLOGY 


BRONCHIOLE    TRACINGS 


379 


heart  respond.  AMiat  coiiclusioii.s  can  yon  draw  from  this ! 
Replace  the  ergamine  into  the  burette  (if  it  was  emptied  out 
before)  and  take  a  normal  record.  Inject  a  dose  of  er- 
gamine (gauge  the  size  by  your  previous  experience — the 
dose  should  be  a  little  larger  than  that  which  was  previously 
just  sufficient  to  produce  a  maximum  effect,  for  the  animal 
becomes  a  little  less  sensitive  all  the  time  to  the  drugs). 


Fig.   315. — Tracing  showing  the  action  of  arecoline,  ergotoxine,    (arecoline')    and  adrenaline 
on   the   bronchioles    and   blood-pressure   in    a    pithed   dog. 


380  EXPEKIMENTAL   PHARMACOLOGY 

Do  you  get  a  satisfactory  record?  Has  the  atropine 
changed  the  influence  of  the  drug  on  the  bronchioles  f  What 
does  this  prove?  How  does  the  action  of  hordenine  com- 
pare with  that  of  adrenaline? 

If  the  animal  is  still  in  a  suitable  condition  (which  is  im- 
probable) you  may  try  to  get  another  contraction  of  the 
bronchioles  from  ergamine  and  then  follow  this  with  an  in- 
jection of  tyramine.  This  drug  is  described  as  acting  in 
many  respects  like  adrenaline.  Will  it  dilate  the  bron- 
chioles ?  Stop  the  artificial  respiration  and  kill  the  animal. 
Dissect  out  both  eyes  and  preserve  them  in  fifty  per  cent 
alcohol  (or  ten  per  cent  formalin)  for  dissection  later. 

EXPERIMENT  CVI. 

Ergotoxine,  Erg-amine.    (Cat,  Guinea  Pig",  Dog,  Rabbit: 
Uterine  Strip.) 

1.  From  one  of  the  animals  mentioned  prepare  a  uterine 
strip  and  arrange  to  record  its  contractions  as  illustrated  in 
Fig.  292  (or  as  in  Fig.  316  if  you  have  the  apparatus).  The 
drum  should  have  a  very  slow  speed. 

When  all  is  ready  take  a  normal  record  and  see  if  you  can 
determine  whether  or  not  the  muscle  is  in  a  strong  tonus, 
and  if  it  is  properly  weighted.  A  good  deal  of  experience 
is  required  to  get  the  best  results  from  the  strips.  Add  one 
or  two  cubic  centimeters  of  ergotoxine  solution  (one  cubic 
centimeter  equals  five  milligrams)  to  the  salt  solution  in 
which  the  strip  is  suspended.  Do  you  get  a  contraction  ?  If 
not  add  some  more  drug.  Wait  and  see  what  happens. 
What  conclusions  can  you  drawl 

After  a  time  change  the  salt  solution  and  allow  the  strip 
to  record  a  normal  contraction.  Do  you  need  to  change  the 
weight?  Now  add  two  cubic  centimeters  of  ergamine  (five 
cubic  centimeters  equal  one  milligram)  to  the  salt  solution. 
What  do  you  observe?    Is  it  necessary  to  add  more  erga- 


XTTERTNE    STRIP    CONTRACTIONS 


381 


mine?  AVhat  conclusions  can  you  draw?  Chang-e  the  salt 
solution  and  then  see  if  you  can  get  a  contraction  of  the 
strip  by  adding  barium  chloride  (in  one -half  per  cent  solu- 
tion) to  the  beaker.  On  what  structures  does  each  of  these 
drugs  act? 


Air  vent 


Fig.  316. — Arrangement  of  apparatus  for  recording  contractions  of  a  uterine  strip, 
intestinal  strip,  or  ring,  etc.  The  metal  water  bath  is  made  of  a  cheap  metal  water  pail 
with  a  heating  rod  soldered  through  the  side  at  the  bottom.  A  short  metal  tube_  is 
soldered  into  a  1-inch  opening  in  the  bottom  to  receive  a  perforated  cork  for  connecting 
with  the   Harvard   muscle  warmer  inside. 


EXPERIMENT  CVII. 
Ergot.     (Cat:    Action  on  Uterus.) 

1.  Secure  a  gravid  cat  as  near  full  term  as  possible.  Un- 
der the  skin  of  the  back  inject  with  a  hypodermic  syringe 
two  cubic  centimeters  of  a  good  fluid  extract  of  ergot.  Put 
the  animal  in  a  quiet  place  and  observe  it  carefully  from 
time  to  time  for  several  hours  following.  Discuss  your  con- 
clusions in  detail. 


382 


EXPERIMEiSTTAL   PHARMACOLOGY 


EXPEEIMENT   CVIII. 

Pituitrin,  Ergamine,  Adrenaline.     (Dog,  Cat,  or  Rabbit: 
Uterine  Contractions,  Blood-pressure.) 

1.  Cats  are  preferred  for  the  experiment.    Observe  care- 
fully the  arrangement  of  the  animal  and  the  apparatus 


Burette  in 
ext  jugular  vein 


Tube  to- 
artificial 
respiration 
machine 


Fig.  317. — Arrangement  of  apparatus  for  recording  contractions  of  the  uterus  in  situ. 
(The  experiment  is  difificult  and  often  yields  unsatisfactory  results.)  A  somewhat  similar 
arrangement  may  be  used  for  recording  intestinal   contractions. 

shown  in  Fig.  317.  The  animal  is  given  .3  to  .4  gram  per 
kilogram  of  body  weight  of  chloretone  (dissolved  in  alcohol) 
by  stomach  tube.  Artificial  respiration  may  be  given 
throughout  the  experiment.  Arrangements  are  made  for 
recording  the  blood-pressure  (omit  this  if  sufficient  appara- 
tus is  not  available),  and  injecting  cannulas  are  connected 
with  one  femoral  vein  and  one  external  jugular.    These  con- 


UTERINE    CONTRACTIONS  383 

tain  ergamine  (ten  cubic  centimeters  equal  one  milligram) 
and  pituitrin  (one  cubic  centimeter  to  five  cubic  centimeters 
of  water — Parke,  Davis  &  Company's  preparation  is  usually 
satisfactory,  but  several  other  extracts  are  on  the  market). 

The  metal  box  in  which  the  animal  is  placed  is  now  filled 
with  0.9  per  cent  salt  solution  which  is  thereafter  kept  at 
39°  C.  by  a  bunsen  burner.  This  prevents  exposure  of  the 
viscera  to  the  cold  air  and  avoids  drying  of  the  tissues. 

The  abdomen  is  now  opened  by  a  long  median  incision 
and  the  intestines  and  bladder  are  pulled  gently  to  one  side 
and  f£stened  beneath  the  salt  solution,  thus  exposing  the 
uterine  horns.  One  of  these  is  followed  up  to  the  ovary 
which  is  gently  dissected  loose  from  its  attachments  (using 
great  care  not  to  disturb  the  blood-vessels)  and  the  distal 
end  of  the  uterine  horn  may  also  be  freed  a  little  from  the 
body  wall  to  permit  freedom  for  its  movements  if  contrac- 
tions occur.  A  myocardiograph  (Cushny's,  Wigger's,  etc., 
or  Fig.  141)  is  now  placed  down  over  the  abdomen.  A  small 
round  needle  is  used  to  pass  two  stitches  of  fine  thread 
through  the  uterine  horn  about  one  inch  apart.  These 
stitches  are  used  to  attach  the  levers  of  the  myocardiograph 
to  the  uterine  horn.  A  very  light  recording  lever  (heart 
lever  or  light  muscle  lever)  is  attached  to  the  myocardio- 
graph and  arranged  to  write  on  the  drum  above  (and 
slightl}^  to  the  left  of)  the  blood-pressure  record.  The  lever 
is  weighted  as  nearly  as  can  be  estimated  to  suit  the 
strength  and  tone  of  each  uterine  horn. 

When  all  adjustments  are  made  a  normal  record  is  taken 
and  then  one-half  cubic  centimeter  (for  a  full  groA\m  cat) 
of  the  pituitary  solution  is  injected.  Do  you  get  a  rise  in 
blood-pressure?  You  should  do  so  and  this  rise  lasts  for  a 
considerable  time.  Wait  for  the  curve  (blood-pressure)  to 
come  back  to  normal.  (Inject  a  larger  dose  if  necessary  to 
get  a  good  record.)  Did  you  get  a  uterine  contraction? 
What  explanation  can  you  offer!  Does  this  have  any  clini- 
cal significance? 


334  EXPEEIMEISTTAL    PHARMACOLOGY 

Now  inject  one-half  cubic  centimeter  of  erganiine  (cat) 
and  see  what  effect  this  has.  Do  you  get  a  fall  in  blood- 
pressure!  Will  the  animal  be  likely  to  die ?  (If  so,  give  it 
a  small  dose  of  pituitrin.)  Did  the  uterus  contract  I  If  so 
on  what  tissues  did  the  drug  act  and  how  were  they  affected? 
Wait  a  while  for  the  animal  to  recover  and  observe  any  later 
actions  of  the  drug.  After  a  time  more  ergamine  may  be 
injected  to  get  another  record. 

If  the  animal  is  still  in  suitable  condition  adrenaline  solu- 
tion may  be  substituted  for  one  of  the  solutions  in  the  bu- 
rette and  a  dose  of  this  drug  injected.  How  does  the  action 
of  adrenaline  on  the  uterus  compare  with,  that  of  the  other 
drugs  given?  AVhat  is  the  innervation  of  the  uterus ?  (See 
Fig.  318.)  Kill  the  animal  by  giving  a  large  dose  of  one  of 
the  drugs  you  have.  AVhat  can  you  say  about  changes  in  the 
innervation  of  the  gravid  uterus  in  the  cat?  Does  this  hold 
also  in  the  human  uterus?  Can  you  find  this  point  in  the 
literature  ? 

This  method  of  recording  uterine  contractions  is  some- 
times used  to  standardize  ergot  preparations  by  comparing 
the  strength  of  the  unknown  solution  with  that  of  a  standard 
preparation.  (For  literature,  see  Edmunds  and  Hale:  loc. 
cit.;  Dale,  Dixon,  Laidlaw,  Barger:  loc.  cit.,  p.  363;  Pitten- 
ger,  P.  S. :  Biochemic  Drug  Assay  Methods,  P.  Blakiston's 
Son  &  Co. ;  also  Dale :  Biochemical  Journal,  iv,  p.  427.) 

EXPEKIMENT  CIX. 

Pituitrin,  Erg-amine,  Levulose,  Adrenaline.    (Dog:  Thoracic 

Duct,  Blood-pressure,  Bladder  Contractions, 

Respiration.) 

(Give  the  dog  one-half  pint  of  cream  to  drink  three  hours 
before  the  experiment.) 

1.  .Arrange  a  dog  for  recording  blood-pressure,  respira- 
tion and  bladder  contractions.    Do  not  disturb  the  viscera 


Pilo  motor  muscle 


Lachrymaj^and 


Ndsal  mucosa ..-  -\ >^-^^ 

-  -  - ' '  !Spheno-palafigang. 

Sublingual yA—^^  P^''°^i^  g/aod^ 
gland    r/j 

Submaxillary  glancA^         U-.0 
5ubmaxlllary(5ublingual}    ^» 
ganglion 


Oall  bladder  and 
ducts. 


\   Cranial  and  Sacral  nerves 

\^  motor  =  red 

nhibitory    •-' 

Ttioracico-lumbar  nerves 

inhibitory=green 

^^  \^ Postganglionic  fibers 

'  are  dotted,  thus— - 

c. 

N.XI 

Sup.  cervical  ganglion 

Thyroid  gland 


Inf.cervical  ganglion 
j;-Ansa  subclavia 

5tejlate  (i?*- Thoracic) 
ganglion 

Sweat  gland 


Small  infest 
Pancreas 


lliocecal 
sptiincter 

Bladder 
Vesical  sphincter 
Urethral  sptiincter, 


Va  so-motor 
fibers 

Pilo  motor  muscle 

Celiac  (Semilunar) 

ganglion{Solarplex) 
Splanchnic  nerves 

'^Sympsthetic  chain 


Lumbar  splanchnics 

Sup.  Mesenteric 

ganglion 


Inf.  Mesenteric 
ganglion 

hypogastric  nerves 


Pelvic(tlYpoqa5tricJnferiHdc)    (  sphincter 
plexus.  [YeSical  S(  rectal  portions)      Pelvic'nerves  (Nervus  eriqens) 


7?   P  HailecK 


Fig.    318. — Schematic   representation    of   the    involuntary    nervous   system. 


Fig.  319. — Dissection  showing  the  method  of  isolating  the  thoracic  duct  at  the  root  of 
the  neck.  Care  should  be  taken  not  to  perforate  the  parietal  pleura  at  the  apex  of  the 
chest  if  it  can  be  avoided  in  making  the  dissection. 


RATE    OF    LYiMPH    FLOW  dOO 

any  more  than  can  be  helped  in  putting  in  the  bladder  can- 
nula. Clamp  the  penis  or  vulva  with  a  hemostat  to  prevent 
urination. 

Consult  Figs.  319  and  302  and  dissect  out  the  thoracic 
duct.  Place  a  cannula  in  it  and  collect  the  lymi)h  as  it  drops 
from  the  small  rubber  tube  placed  on  the  cannula.  The 
cannula  must  be  very  small,  the  opening  in  the  end  should 
be  about  the  size  of  a  ver}^  small  thread  and  the  outside  of 
the  tip  of  the  cannula  should  not  exceed  %2  or  %4  of  an  inch 
in  diameter.  Try  to  avoid  penetrating  the  chest  cavity  at 
the  apex  in  dissecting  out  the  duct.  If  the  chest  is  opened  it 
may  be  necessary  to  give  artificial  respiration  during  the 
rest  of  the  experiment.  If  the  cream  has  reached  the  in- 
testine and  is  being  absorbed  well  (two  to  three  hours  after 
meal)  the  thoracic  duct  in  the  neck  should  be  of  a  whitish  or 
5^ellowish-white  color  and  in  an  average  sized  dog  will  be 
about  YiQ  or  %2  of  an  inch  in  diameter.  The  duct  is  com- 
posed of  exceedingly  thin  and  delicate  tissue  and  can  be 
easily  torn  off  and  lost  in  the  dissection,  the  student  per- 
haps not  seeing  it  at  all  at  any  time.  A  little  pressure  mil 
compress  the  duct  and  check  all  out-flow  from  it. 

(Those  students  who  have  sufficient  technical  skill  may 
also  insert  a  cannula  in  the  l^miphatic  duct  coming  from  the 
head  and  collect  l3miph  from  both  ducts  at  the  same  time. 
There  is  a  very  marked  difference  and  the  experiment  is 
well  worth  doing.) 

The  injecting  burettes  contain  pituitrin  (1  to  5 — Parke, 
Davis  &  Co.),  ergamine  (ten  cubic  centimeters  equal  one 
milligram)  and  adrenaline  (1:10,000). 

When  all  adjustments  are  made  take  a  normal  tracing, 
watch  the  pupils  and  inject  one  cubic  centimeter  of  pituitrin 
solution  (dog,  eight  kilos  or  more).  Do  you  get  a  rise  in 
pressure,  contraction  of  the  bladder  and  a  change  in  the 
rate  and  depth  of  respiration?  If  the  dose  was  sufficient,  as 
it  probably  was,  allow  the  animal  to  return  to  normal  and 
wait  until  the  normal  rate  of  hmipli   flow   is    determined 


386 


EXPERIMENTAL   PHAEMACOLOGY 


(number  of  drops  per  minute).  The  rubber  tube  or  cannula 
may  become  clogged.  If  so  pass  a  stiff  twine  string  down 
the  cannula  and  try  to  remove  the  clot. 

The  pituitrin  is  now  emptied  out  and  the  burette  is  filled 


External 
jugular  vein 

Precava 
Axillary  gi 


Bronchial  glands 
receiving  lymph 
lungs 

Lymphatic  vessels 
from  liver 


5mall 
intestine 


Large  intestine 


Vessel  from 
abdominal  wall 
Inguinal  glan 


■MailecH 


—Superficial  lymphafics  from  head 
Submaxillary  lymph  glands 

Laryngeal  glands 
Tracheal  trunks 
Cervical  glands 
^Superficial  lymphatics  from  limb 

Junction  of  thoracic  duct  with 
,  ,    .  .       tracheal  trunk 

Subclavian  vein 

Lymphatic  trunk 

eep  lymphatic  vessels  from  limb 
Lymphatics  from  thoracic  wall 

— Vessel  from  diaphragm 
Thoracic  duct 

Pancreas  Aselli 

Lymph  trunk  from  pancreas  Aselli 
to  thoracic  duct 

-Receptaculum  chyli 

Lacteal  vessels  and  glands  of 
mesentery 

Lumbar  glands 

Iliac  glands 

Vessels  from  limb 
Lymphatics  from  skin  of  leg 


Fig.    320. — Diagrammatic    representation    of    the    lymphatic    system    in    a    cat.       (Partially 

adopted   from   Davison.) 


LYMPH    FLOAV PITUITRUST  387 

with  levulose  solution  (five  or  ten  per  cent).  In  small  re- 
peated doses  (one-half  or  one  cubic  centimeter)  several 
cubic  centimeters  of  the  levulose  solution  are  injected.  Wait 
then  and  see  how  the  rate  of  lymph  flow  is  affected.  (How 
is  the  lymph  flow  from  the  head  affected?  Is  this  rate  of 
flow  maintained  or  does  it  decrease  after  a  time!) 

After  some  time  note  the  rate  of  lymph  flow  and  adjust 
all  writing  points.  Observe  the  pupils  and  inject  one  cubic 
centimeter  of  ergamine.  Do  you  get  satisfactory  records"? 
If  the  dose  was  too  small  wait  a  while  and  inject  a  larger 
one  to  get  good  results.  How  did  the  bladder  respond? 
How  does  this  compare  with  pituitrin  ? 

Inject  adrenaline  and  see  how  this  affects  the  lymph  flow, 
bladder,  pupil  and  respiration. 

With  what  other  lymphogogues  are  you  acquainted  ?  You 
may  try  some  of  these  on  the  animal  if  it  is  still  in  suitable 
condition.  Kill  the  animal  with  an  injection  of  some  of  the 
drugs  you  have.  Always  get  a  death  record  in  such  cases 
and  see  which  stops  first,  the  heart  or  the  respiration. 

How  may  drugs  affect  the  rate  of  secretion  or  of  flow  of 
l^rniph?  How  is  the  formation  of  lymph  controlled?  What 
can  you  say  about  the  innervation  of  the  lymphatics  1  How 
does  atropine  affect  lymph  secretion? 

EXPERIMENT  CX. 
Pituitrin.     (Frog:     Capillary  Circulation.) 

1.  As  in  Experiment  C,  page  361,  arrange  a  frog  for  ob- 
serving the  capillary  circulation  in  the  web  of  the  foot  (Fig. 
305).  Observe  carefully  (for  comparison)  the  normal  rate 
of  capillary  flow  and  then  inject  one-half  cubic  centimeter 
(or  more)  of  pituitrin  under  the  skin  of  the  frog's  back. 
From  moment  to  moment  again  observe  the  circulation  in 
the  web  and  see  if  any  change  occurs.  If  you  note  a  change 
keep  a  careful  w^atch  on  the  animal  from  time  to  time  for 


EXPERIMENTAL   PHARMACOLOGY 


two  or  three  hours  and  see  if  there  is  a  return  to  normal. 
Keep  the  animal  covered  with  a  thin  layer  of  wet  cotton. 

EXPERIMENT  CXI. 

Pituitrin.     (Frog  or  Turtle:    Heart  Tracing.) 

1.  Pith  a  frog  or  turtle  and  take  a  normal  heart  tracing 
shomng  vagus  inhibition.  Irrigate  the  heart  with  some 
pituitrin  solution  (1  to  5)  and  determine  the  action  of  the 
substance  on  the  heart.  Is  the  inhibitory  apparatus  in- 
volved in  any  way?  How  is  the  nmsculature  of  the  heart  af- 
fected? 

EXPERIMENT  CXII. 
Pituitrin.     (Turtle:     Lung  Tracing.) 

1.  Arrange  a  turtle  for  recording  lung  tracings.  Stimu- 
late one  vagus  nerve  and  see  if  you  get  a  contraction  of  the 


i^^^^-^a^Ayr^. 


mulummnmnaiummuiiumam 


Fig.   321. — Turtle  lung  tracing  showing  the  action   of  pituitrin. 

lung.  The  magnification  of  the  tambour  tracing  should  be 
large.  Take  a  normal  and  inject  into  the  heart  one  cubic 
centimeter  of  pituitrin  solution  (1  to  5),  What  conclusions 
can  you  draw  from  your  results  ? 


ACTION    OF    PITUITRIjST 


389 


j9jiU2^^  /-r. 


i^c^;-  /SM^:-(%^&tJUayudiuU 


^^diAAAA.  2'^  .A>ii<^' 


Mmw^iMtmmmml^ 


Fig.   322. — Tracing  showing  the  action  of  pituitrin   on  the  uterine   contractions   and   blood- 
pressure  in  a  dog.     Made  by  Barbour's  method. 


390  EXPERIMENTAL   PHARMACOLOGY 

EXPEEIMENT  CXIII. 

Pituitrin.    (Guinea  Pig,  Cat,  Dog,  Rabbit:    Uterine  Strip.) 

1.  Cats  or  guinea  pigs  are  preferred.  Prepare  a  uterine 
strip  and  record  its  contractions.  (See  Experiment  CVI, 
also  Figs.  292  and  316.)  After  the  strip  is  properly 
weighted  and  a  short  record  has  been  taken  add  to  the  solu- 
tion surrounding  the  strip  one  cubic  centimeter  of  pituitrin 
(1  to  20).  Do  3'ou  get  a  satisfactory  contraction?  Wait  a 
while,  the  drum  runs  at  a  very  slow  speed.  If  after  some 
minutes  no  change  has  been  produced  replace  the  salt  solu- 
tion with  a  fresh  supply  and  inject  a  larger  dose  of  pituitrin. 
Could  you  standardize  the  size  of  the  dose  by  the  size  of 
the  contraction  the  uterine  strip  gives  1  If  you  had  a 
standard  preparation  of  pituitary  extract  could  you  com- 
pare ^\ith  this  the  strength  of  an  unknown  sample  ?  If  one- 
half  as  large  a  dose  of  the  unknown  sample  were  required  to 
give  a  tracing  three  inches  high,  as  was  required  of  the 
standard  preparation,  what  could  you  say  of  the  relative 
strengths  of  the  two  samples?  How  much  would  you  dilute 
the  unknown  preparation  to  bring  it  to  the  same  strength 
as  the  standard"?  This  is  essentially  the  method  commonly 
used  to  standardize  (assay)  pituitary  preparations  for  the 
market.  (For  literature,  see  Dale  and  Laidlaw:  Journal 
of  Physiology,  1910-11,  xli,  p.  318;  Dale  and  Dixon:  ibid, 
1909,  xxxix,  p.  25 ;  Dale  and  LaidlaAv :  Journal  of  Pharma- 
cology and  Experimental  Therapeutics,  1912,  iv.  p.  75; 
Hamilton,  H.  C. :  Journal  American  Pharmaceutical  Asso- 
ciation, 1912 ;  Roth,  G.  W. :  Bulletin  Hygiene  Laboratory, 
No.  100;  also  Journal  Pharmacology  and  Experimental 
Therapeutics,  1914,  v.  p.  557;  Fenger:  Journal  Biologic 
Chemistry,  1916,  xxv,  p.  417 ;  Frankl-Hochwart  und  Froh- 
lich:  Archiv  fiir  experimentelle  Pathologic  und  Pharma- 
kologie,.  1910,  Ixiii,  p.  347 ;  Hamilton  and  Rowe :  Journal  of 
Laboratory  and  Clinical  Medicine,  1916,  ii,  p.  120.) 


PITUITRIlSr,    ADRENALINE,    ATROPINE 


391 


EXPERIMENT  CXIV. 

Pituitary  Extract,  Adrenaline,  Atropine,  Barium. 
Bronchial  Contraction.) 


(Dog: 


1.  By  one  of  the  methods  previously  used  arrange  a  dog 
for  recording  bronchial  contractions.  When  all  adjust- 
ments are  made  stimulate  the  vagus  nerves  and  see  how  the 


SSfju^t^l-Qj^fli^'^tXia't'^ 


iiiiiiiimiiiiiiiiiiiiiiiiiiiiiiifiiiiiiffliml^rmT^^ 


IIHIItlllll 


Fig.   323. 


-Tracing  showing  the   action   of   pituitrin    on  the   bronchioles  and   blood-pressure 
in  a  spinal  dog. 


bronchioles  react,  then  inject  two  cubic  centimeters  (dog — 
eight  to  ten  kilos)  of  pituitrin  solution  (1  to  5).  Do  you 
get  a  satisfactory  record!  AVhat  is  the  action  of  pituitary 
extract  on  the  bronchioles?  Is  this  a  muscular  or  nervous 
affair?  What  action  has  pituitrin  on  the  sympathetic 
nervous  system?  How  does  this  compare  A^dth  adrenaline 
and  tyramine? 


392  experime:ntal  pharmacology 

This  dose  was  probably  large  enough  (for  some  animals 
too  large — the  instructor  may  advise  you  about  this)  but 
if  you  think  advisable  try  another  dose  to  see  if  you  can 
get  more  satisfactory  results. 

When  the  animal  recovers  give  one  cubic  centimeter  of 
atropine,  then  stimulate  the  vagi  and  see  if  the  heart  is 
inhibited  (how  are  the  bronchi  affected!).  Give  a  little 
adrenaline  to  revive  the  animal  and  inject  another  dose 
(estimate  the  size)  of  pituitrin.  How  are  the  bronchioles 
affected  now  after  the  atropine?  Would  you  advise  the 
iise  of  pituitrin  in  bronchial  asthma  !  How  do  your  results 
in  this  experiment  compare  with  those  obtained  on  the 
turtle  lung?  Kill  the  animal  Avith  a  large  dose  of  barium 
chloride  solution  (one-half  per  cent).  How  does  this  affect 
the  bronchi? 

EXPERIMENT  CXV. 

Pituitrin,  Adrenaline,  Aconitine.     (Dog:    Urine  Secretion, 

Intestinal  Contractions,  Blood-pressure,  and 

Respiration.) 

1.  Arrange  a  dog  for  recording  the  blood-pressure,  res- 
piration and  intestinal  contractions  (by  the  fingercot-bu- 
rette  method).  The  injecting  burettes  contain  pituitrin  (1 
to  5)  and  adrenaline  (1:10,000).  Carefully  isolate  both 
ureters  (Fig.  162)  and  place  a  ureteral  cannula  (Fig.  213) 
in  each.  Arrange  the  cannulas  to  collect  the  urine  flow 
in  a  beaker.  Record  on  the  drum  the  rate  of  drop  flow  with 
a  signal  magnet  (worked  by  a  simple  key  in  circuit  Avith  a 
dry  cell).  Close  the  abdomen  Avith  hemostats  and  Avait  ten 
or  twenty  minutes  to  get  the  normal  rate  of  urine  flow. 
(The  drum  should  have  a  very  sIoav  speed.) 

When  the  normal  rate  of  urine  flow  has  been  determined 
(if  no  urine  is  excreted  after  twenty  minutes  go  on  AAdth  the 
experiment  and  Avatch  for  the  flow  to  begin),  take  a  nor- 
mal record  and  then  inject  one  cubic  centimeter  (for  eight 


PITUITRIX    AND    ACONITINE  393 

to  ten  kilo  dog)  of  pituitrin  solution.  How  does  this  affect 
the  blood-pressure?  What  happens  to  the  respiration? 
Is  this  a  central  or  a  peripheral  action?  After  the  records 
return  to  normal  (see  that  all  pointers  are  recording 
properl}^)  inject  a  second  dose  of  one  cubic  centimeter  and 
compare  the  results  produced  b}^  this  with  those  obtained 
from  the  first  injection.  As  soon  as  the  records  again  reach 
the  normal  (keep  the  anesthesia  regular)  inject  a  third  dose 
of  one  cubic  centimeter.  Does  the  animal  become  more  or 
less  sensitive  to  the  drug?  Is  the  rate  of  urine  flow  affected 
in  any  way?  If  so  how  do  you  explain  it?  Is  the  change 
as  great  as  you  expected?  How  does  it  compare  with  caf- 
feine or  sodium  sulphate?  Continue  giving  pituitrin  until 
five  or  six  (or  more)  cubic  centimeters  have  been  given, 
watching  for  changes  in  the  rate  of  urine  flow  in  the  mean- 
time. Do  the  intestines  show  any  signs  of  increased  ac- 
tivity? If  so  is  this  a  nervous  or  muscular  affair?  Inject 
some  adrenaline  and  see  how  this  affects  the  urine  flow  and 
intestinal  records.  Do  you  see  any  signs  of  a  tolerance 
being  developed  for  the  pituitrin?  If  so  to  what  is  it  due? 
Does  this  occur  with  any  other  drugs?  Could  you  stand- 
ardize an  unkno"s\ai  pituitary  extract  by  comparing  the  ac- 
tion of  various  sized  doses  of  the  unknown  mth  a  standard 
dose  of  a  standard  pituitary  extract  on  the  blood-pressure? 
This  method  is  sometimes  used  to  assay  pituitary  extracts. 
In  that  case  small  sized  doses  are  given  and  a  considerable 
period  of  time  (fifteen  minutes  or  more)  is  allowed  to  elapse 
between  each  two  injections. 

If  the  animal  is  still  in  fair  condition  place  a  solution  of 
aconitine  "potent"  {ten  cubic  centimeters  equal  one  milli- 
gram) in  the  burette  and  determine  what  is  tlie  very  least 
amount  of  the  substance  required  to  kill  the  animal.  The 
injections  must  be  made  cautiously.  AVatcli  for  postmortem 
intestinal  contractions.  Open  the  chest  and  see  if  the  heart 
is  fibrillating. 


394  EXPERIMEiSTTAL    PHARMACOLOGY 

EXPERIMENT  CXVI. 

Pituitrin,  Adrenaline,  Vanadium.     (Dog:    Pulmonary 
Blood-pressure.) 

1.  In  the  manner  described  in  Experiment  CIV,  p.  369 
(also  in  Experiment  LXXVII,  p.  310)  arrange  a  dog  for 
recording  pulmonary  blood-pressure.  The  injecting  bu- 
rettes contain  pituitrin  (1  to  5)  and  adrenaline  (1:10,000). 
When  all  adjustments  are  made  take  a  normal  record  and 
then  inject  one  cubic  centimeter  pituitrin  solution.  Do  you 
get  a  change  in  pulmonary  pressure?  Would  you  advise 
the  use  of  pitnitary  extract  in  a  pulmonary  hemorrhage 
from  a  tuberculous  lesion?  What  structures  are  affected 
by  the  drug  in  the  lungs  1  Would  the  drug  be  advisable  in 
bronchial  asthma! 

After  a  record  showing  the  action  of  pituitrin  on  the  pul- 
monary pressure  has  been  obtained  get  the  animal  into  as 
good  condition  as  possible  and  fill  one  burette  with  a  solu- 
tion of  sodium  ortho vanadate  (two  per  cent — when  the  drug 
is  dissolved  in  the  water  the  solution  is  slightly  alkaline). 
Add  a  very  small  amount  of  hydrochloric  acid  to  neutralize 
the  alkalinity,  A  bright,  clear,  orange-yellow  solution  will 
be  produced.  Take  a  normal  record  and  inject  two  cubic 
centimeters  of  the  vanadium  solution.  Was  the  dose  large 
enough!  If  not,  possibly  you  can  still  get  another  record 
with  a  larger  dose.  Kill  the  animal  with  the  vanadium 
solution.  What  conclusions  can  you  draw  from  the  experi- 
ment?   On  what  structures  does  the  vanadium  act? 

EXPERIMENT  CXVII* 

Dissection  of  the  Eye. — Its  Anatomy  and  Pharmacology. 

Consult  Figs.  324  and  325.  It  is  advisable  to  read  the 
section  on  the  anatomy  of  the  eye  in  some  good  text-book  on 
anatomv. 


*It  is  expected  that  this  experiment  may  be  performed   on  a  day  when  no   other  experi- 
mental material   is  available. 


6phmder 
iridis 

Pupil 

Radial     _, 
(dilator)  ^ 
muscle 
of  iris 

To  ciliary  muscle 
ciliary  muscle  \  Long  aUary 


Dilatation 
of  pupil 

Contraction 
of  pupil 


mil 

Ciliary  muscle  (accommodation) 

'^- Kill  (Contraction  of  pupil) 

"^  Electrodes 

(Dilatation  or  constriction  of  pupil; 
contraction  of  ciliary  muscle) 


Electrodes' 
{Dilafafion  of  pupil, 
openinq  wider  of  eyelids, or 
bulqinq  forward  of  eyeball) 

Out'Qoinq  sympathetic  rami  communicantes^ 


Sensory  qanq/ion  cell 
(Sensory  nervesfrom  eye  reqior) 

^'"^  '  ^Nucleusof^ 

origin  iE— nerve 

Corpora 
'  Quadrigemina 
■Position  (:')  of 
pupillodilator 
center 

N.vn 

N.VIIl 

\ 

N.VI 

Medulla 

oblongata 
Descending  symp- 
athetic fibres 
in  the 
3pindl  cord 
(sp.medulla) 

Cat,  dog,  rabbit 
I  Thoracic 

n 

Ul 

itallesk 


Fig.    324. — Schematic   representation   of   the   innervation   of   the  eye.      Postganglionic   fibers 
are  shown  as  broken  lines. 


y 


Endings  of  N.  V (Sensory)  in  tissues  of  the  eye 

Endings  of  N.  Ill  in  \  /Cornea 

sphincter  pupillae  musde\  /  /Anterior  chamber  (Aqueous humor) 
5inus  venosus  sclerae  W^==='''"~^"=^  /Posterior  chamber 

{Canal  of5chlemrn)-jO<^''~~'~^fS^^  fiber  in 

<C   4.-  r         y^^X -— ^^•^^^~^      dilator  pupillae  muscle 

ifiH^^  ^    c^S^^tLenrm^^^^"^'"9  ^t  ^- '" '"  ^'''^''y 

-Tendon  of  rectus 
muscle 

Retina 

Choroid 

Sclera 


Sheath  of  optic 
nerve 
Arte  rid  centrdlis 
retinae 


Sensory  fiber  from  N.V 
to  the  eye  regions 

Postganglionic  fibers 
are  dotted  thus  — 


Fovea  centra/is 

Ciliary  ganglion 

'^^Fiber  to  ciliary  muscle  (Accommoddtion) 

Fiber  to  sphincter  pupillae  muscle 
^^  ^ — ~^^5up.ceryicai  ganglion 

T~  ~y^^ — -"^     {:)—  ^^^^'^^  ^ymp- 

I      1^ ___- ^          cord 

Post  gang.  symp.  fiber  to  dilator  pupillae 

muscle 


Fig.   325. — Diagrammatic   representation  of  the  .structure  and  innervation   of  the  eye. 


ANATOMY   AND    PHARMACOLOGY    OF    EYE  395 

The  eyes  saved  previously  froin  dogs  may  l)e  used  for . 
dissection,  or  eyes  from  hogs  or  cattle  may  be  secured  (in 
weak  formalin  solution)  from  the  slaughter  house. 

Dissect  away  the  fascia  from  the  outside  of  the  eye-ball 
and  isolate  and  identify  the  extrinsic  muscles.  Are  there 
any  variations  in  these  in  different  species  of  animals? 
What  is  the  innervation  of  these  muscles? 

Isolate  the  optic  nerve  and  follow  it  to  the  sclera.  Dis- 
sect off  the  extrinsic  muscles  and  free  the  eye  from  fascia. 
Do  you  have  a  right  or  a  left  eye  1  Locate  on  the  eye-ball  a 
point  directly  outside  the  area  which  should  be  occupied  by 
the  fovea  centralis.  Do  the  lower  animals  possess  this 
structure  ?  What  is  its  function  ?  Over  this  area  cut  a  win- 
dow about  one-eighth  inch  square  in  the  sclerotic  doA\ai  to 
the  choroid.  Hunt  for  the  fibers  of  the  ciliary  nerves  which 
pass  forward  in  the  interspace  between  the  sclera  and  the 
choroid.  In  the  normal  animal  what  reactions  would  fol- 
low electrical  stimulation  of  these  fibers!  AVith  care  en- 
large the  opening  in  the  sclerotic  a  little  and  then  dissect 
awaj^  the  choroid  which  forms  the  floor  of  the  opening. 

Use  great  care  not  to  penetrate  the  retina  which  will  be 
exposed  when  the  choroid  is  removed.  If  the  eye  has  not 
been  long  in  the  formaldehyde  or  alcohol  the  cornea  and 
lens  may  still  be  transparent  enough  to  allow  an  image  to 
be  formed  on  the  retina  (this  is  best  shown  in  fresh  eyes). 

Take  a  sheet  of  brown  wrapping  paper  a  foot  square  and 
roll  it  into  a  tube  with  an  opening  just  large  enough  to  hold 
the  eye  at  one  end.  Place  two  rul:>ber  bands  around  the 
tube  to  prevent  unrolling.  The  eye  is  placed  in  the  end  of 
the  tube  with  the  opening  in  the  sclerotic  and  choroid  coats 
turned  outward,  i.e.,  the  cornea  and  lens  are  directed  to 
look  through  the  tube.  Point  the  open  end  of  the  tube  to- 
ward an  incandescent  light  or  bright  window  and  watch 
carefully  in  the  exposed  area  at  the  back  of  the  eye  for  an 
image  of  the  light  or  window.  If  you  detect  any  image 
state  fully  its  characteristics  and  peculiarities. 


396  EXPERIMENTAL   PHARMACOLOGY 

Examine  the  cornea  and  pupil.  Place  the  eye  in  a  pan  of 
water  and  make  an  incision  around  it  in  the  line  of  the 
equator  so  as  to  separate  the  front  half  from  the  rear  half. 
The  incision  may  go  through  all  three  coats,  but  the  vitre- 
ous humor  should  not  be  disturbed.  Lift  off  the  rear  half 
of  the  coats  and  look  into  the  cup  thus  formed.  What  color 
is  the  retina?  Of  what  is  it  composed  I  What  drugs  act  on 
the  structural  elements  of  the  retina?  What  particular 
parts  of  the  retina  are  involved  in  this  action?  Define  the 
optic  disc  and  the  central  artery  of  the  retina.  What  is 
meant  by  the  optic  cup?  What  relation  does  it  bear  to  the 
macula  lutea  ?  Separate  the  sclerotic  from  the  choroid  and 
define  the  lamina  fusca.  Hunt  for  the  ciliary  nerves  (and 
vessels)  between  the  sclera  and  choroid.  How  do  these 
nerves  get  into  the  eye-ball?  Define  the  lamina  cribrosa 
sclerge. 

Now  take  up  the  anterior  half  of  the  eye  to  which  the 
vitreous  humor  probably  remains  attached.  Look  for  the 
hyaloid  membrane.  What  are  its  functions  ?  To  Avhat  is  it 
attached?  Gently  separate  the  vitreous  humor  from  the 
lens  and  ciliary  processes  and  let  it  float  in  the  water.  De- 
scribe its  color,  consistency  and  functions.  Have  you  seen 
anything  of  the  ora  serrata?  Noav  examine  the  ciliary 
processes  and  discuss  their  relations  to  the  choroid  and  to 
the  lens.  Where  are  the  ciliary  muscle  fibers  ?  What  is  the 
innervation  of  this  muscle?  What  are  its  points  of  origin 
and  of  insertion  ?  What  are  its  functions  ?  What  drugs  act 
on  it  and  how  do  they  act  ? 

AVith  care  dissect  away  a  small  sector  of  the  suspensory 
ligament  of  the  lens.  What  is  the  canal  of  Petit?  Where 
are  the  spaces  of  Fontana  located  and  what  is  their  func- 
tion? What  drugs  may  influence  this  function  and  how? 
What  is  the  canal  of  Sclemm  ?  Eemove  the  entire  lens.  If  it 
is  sufficiently  transparent  lay  it  over  some  small  print  and 
see  if  the  letters  can  be  seen  through  the  lens.  How  many 
forms  of  lenses  do  you  know?    To  which  of  these  does  the 


THE    EYE AMYL    XITRITE  397 

crystalline  lens  belong"?  How  is  the  eye  focused  for  vary- 
ing distances!  What  part  does  the  lens  play  in  this  joroc- 
ess?  Make  two  diagrams  to  show  these  actions.  AVhat 
drugs  may  influence  these  processes  and  how  do  the  drugs 
act! 

Examine  the  iris.  Locate  the  anterior  and  posterior 
chambers.  With  what  is  each  filled?  May  drugs  influence 
these  chambers  in  any  way?  If  so  how?  Can  3^ou  find  any 
evidence  of  the  existence  of  dilator  muscle  fibers  for  the 
pupil?  Where  would  you  look  for  these?  What  is  the  in- 
nervation of  this  set  of  fibers?  What  drugs  act  on  the 
dilator  mechanism  and  where  and  how  do  these  drugs  act  ? 
How  is  the  intraocular  pressure  controlled?  How  may 
drugs  influence  this  ?  Can  you  find  the  sphincter  muscle  of 
the  iris?  How  is  this  muscle  innervated?  What  part  does 
it  play  in  accommodation?  What  drugs  may  affect  this 
muscle  and  how  and  Avhere  do  they  act?  Compare  the  iris 
of  a  bird  with  that  of  a  mammal  as  regards  the  action  of 
atropine,  pilocarpine  and  cocaine.  Make  a  diagram  show- 
ing the  structure  and  innervation  of  the  eye  and  indicate 
thereon  Avith  ledger  lines  the  points  where  all  drugs  which 
atfect  the  eye  and  with  which  3^ou  are  familiar  act.  Indi- 
cate the  nature  of  these  actions  with  a  plus  (  +  )  sign  for 
stimulation  and  a  minus  ( — )  sign  for  depression  and  paral- 
ysis. Describe  all  nervous  paths  and  elements  involved  in 
the  pupillary  light  reflex.  What  is  an  Argyll-Robertson 
pupil  ? 

EXPERIMENT  CXVIII. 

Amyl  Nitrite.     (Student:   Plethysmographic  Record, 
General  Action.) 

1.  Arrange  your  apparatus  for  taking  a  volume  record 
of  the  arm  as  shown  in  Fig.  326.  When  all  adjustments  are 
made  fold  a  handkerchief  over  a  three  (or  five)  minim  amyl 
nitrite  pearl  and  prepare  to  break  the  pearl  by  squeezing 


398 


EXPEEIMENTAL   PHAKMACOLOGY 


it  with  a  pair  of  pliers.  (Pearls,  or  ampoules,  are  now  pre- 
pared by  several  firms  already  covered  by  cloth  so  that 
glass  particles  can  not  fly  off  from  the  ampoule  when  it  is 
broken.)  Bring  the  pearl  (or  ampoule)  up  close  to  the  sub- 
ject's nose  and  allow  the  vapors  of  the  drug  to  be  breathed 
in  at  once  as  the  glass  container  is  snapped  by  the  pliers. 
Be  sure  you  already  have  a  normal  plethysmographic 
record  started  (on  a  slow  drum)  before  the  pearl  is  broken. 


Fig.  326. — Plethysmograph  for  recording  volume  changes  in  the  hand  and  forearm. 
The  rubber  band  that  connects  the  plethj'smograph  to  the  arm  may  be  made  of  the  wrist 
or  arm  portion  of  a  rubber  glove   (which  may  be  bought  in  a  ten  cent  store). 

The  subject  should  be  sitting  (or  lying)  in  a  perfectly  com- 
fortable position  so  that  he  will  not  move  the  hand  into 
and  out  of  the  plethj'smograph  while  the  record  is  being- 
taken.  The  drug  is  very  volatile  and  in  a  few  seconds  it 
will  have  practically  all  disappeared. 

What  does  your  record  show?  How  do  you  explain  the 
results?  What  general  sensations  does  the  subject  feel? 
W^atch  his  face  and  neck  closely  for  any  flushing  of  the  skin 


ACTIOiSr    OF    AMYL    NITRITE 


399 


that  may  occur.  Count  his  pulse  and  compare  with  the 
normaL  Be  sure  to  observe  his  rate  and  depth  of  breath- 
ing as  the  drug  is  inhaled.  How  do  you  account  for  the 
changes  observed? 


EXPERIMENT  CXIX. 
Amyl  Nitrite.    (Student:    Pulse  Tracing.) 

1.  Attach  a  sphygmograph  to  the  wrist  as  sho^vn  in  Fig. 
327.  Take  one  or  tw^o  normal  tracings  and  then  prepare  a 
strip  of  paper  ready  to  record  the  action  of  amyl  nitrite  on 


Fig.  327. — Dudgeon's  sphygmograph  arranged  for  recording  tracings  from  the  radial  pulse. 


the  pulse.  The  subject  should  be  in  a  perfectly  comfort- 
able position.  When  all  is  ready  break  the  pearl  or  am- 
poule and  let  the  subject  inhale  the  vapors.  When  the  ef- 
fects come  on  markedly  (in  about  ten  seconds)  start  the 
clock  work  and  run  the  paper  through  rapidly  to  record  the 
changes  in  the  form  of  the  pulse  curve.  What  can  you  say 
about  the  dicrotic  wave?  What  is  its  origin  and  sig- 
nificance?   HoAv  does  amyl  nitrite  affect  it?    What  other 


400 


EXPERIMENTAL    PHARMACOLOGY 


■  rJ/otAn^ 


Fig.   328. — Tracing  made  with  Dudgeon's  sphygmograph   showing  the  normal   pulse   record 
and   a  pulse   record  as   affected   by   inhaling  amyl   nitrite. 

changes  are  produced  in  the  pulse  curve?    How  does  the 
drug  produce  these? 

EXPERIMENT  CXX. 


Amyl  Nitrite.     (Student:     Corpuscles  in  Retinal  Vessels.) 

1.  Obtain  a  piece  of  blue  glass  about  four  inches  square. 
(It  is  often  better  to  use  two  pieces  of  glass  placed  together 
to  intensify  the  color.)  Let  the  subject  of  the  experiment 
lie  down  at  perfect  rest  on  his  back  before  a  large  window 
through  which  he  can  see  a  large  expanse  of  clear  blue  sky. 
(The  sun  should  not  shine  on  the  student's  face  or  on  the 
blue  glass  plate.)  The  student  now  holds  the  glass  near 
his  face  and  looks  through  the  glass  up  into  the  clear  sky. 
He  accommodates  his  eyes  for  a  long  distance  and  remains 
as  perfectly  at  rest  as  possible.  Presently  a  considerable 
number  of  small,  almost  circular,  shadoAvy,  ill-defined  ob- 
jects will  begin  to  appear  in  the  field  of  vision.  These  ob- 
jects have  a  rapid,  squirming  motion,  reminding  one  of  the 
movements  of  an  angle  worm  in  water.  The  objects  flit 
into  sight  suddenl3^  squirm  about  for  an  instant  and  then 
suddenly  disappear.     These  objects  are  believed  to  be  the 


ACTIOIT    OF    AMYLJ  NITRITE  401 

shadows  of  the  corpuscles  circiilgitiiig  in  the  capillaries  of 
the  retina  in  front  of  the  rods  and  cones.  Observe  carefully 
(but  do  not  try  to  fix  the  eye  on  any  given  point)  about  how 
numerous  these  objects  are  in  the  field  of  vision.  If  the 
number  were  suddenly  doubled  or  reduced  by  half,  could 
you  detect  the  difference  f  Do  not  strain  your  eyes  in  watch- 
ing for  the  objects  as  efforts  in  this  direction  will  avail 
nothing  and  may  even  appear  to  decrease  the  number  of 
shadows  visible.  Can  you  make  out  the  shape  of  individual 
corpuscles?  Do  the  shadows  appear  to  move  in  set  paths, 
i.e.,  within  the  lumen  of  the  capillaries?  Do  any  two  or 
more  shadows  follow  the  same  course  as  near  as  you  can 
judge?  When  the  student  has  learned  the  appearance  of 
these  shadows  well  and  can  readily  estimate  an}^  consider- 
able change  in  their  number  then,  as  the  subject  keeps 
watching  the  shadoAvs,  an  amyl  nitrite  pearl  is  broken  near 
his  nose  and  he  quickly  breathes  in  its  vapors.  A¥atch  his 
respiratory  movements  closely.  Does  his  face  flush?  The 
subject  should  not  know  what  change  to  expect  in  the  num- 
ber or  movement  of  the  corpuscle  shadows  seen  by  him. 
In  what  ways  may  amyl  nitrite  influence  the  appearance  of 
these  shadows?    Explain  in  detail. 

EXPERIMENT  CXXI. 
Amyl  Nitrite.    (Student:    Retinal  Blood  Vessels.) 

1.  Through  the  center  of  a  stiff,  opaque  card  (calling 
card,  or  smoked,  varnished  drum  paper)  a  pin  hole  is 
made.  The  card  may  be  about  two  by  three  inches  in  size. 
The  subject  sits  down  at  perfect  rest  in  front  of  a  window 
through  which  he  can  see  a  considerable  expanse  of  clear, 
blue  sky.  A  few  objects,  as  the  top  of  a  building  or  a  tree, 
may  well  be  located  about  200  to  400  feet  in  front  of  the 
window,  so  the  subject  by  lowering  his  field  of  vision  a  little 
can  see  the  upper  part  of  these  objects.     The  purpose  of 


402  EXPERIMENTAL   PHARMACOLOGY 

this  is  to  give  the  student  a  chance  to  knoAv  when  he  has  his 
eyes  focused  for  a  long  distance  (with  which  point  most 
students  are  unfamiliar). 

The  subject  looks  out  into  the  clear  sky  (avoid  sunlight) 
and  holds  the  card  in  his  right  hand  in  front  of  and  near 
to  his  right  e^^e.  The  left  eye  is  closed.  The  right  eye  looks 
through  the  pin-hole  in  the  card  and  is  focused  for  a  long 
distance,  i.e.,  the  ciliary  muscle  is  completely  relaxed  and 
the  pupil  is  dilated.  The  card  is  now  moved  in  a  rotary 
manner  in  such  a  way  that  the  pin-hole  will  describe  a  small 
circle  in  front  of  the  pupil.  The  diameter  of  this  circle 
should  be  about  one-eighth  of  an  inch  or  less  and  the  circu- 
lar movement  should  be  repeated  at  the  rate  of  about  two 
or  three  times  per  second.  Thus  a  small  ray  of  light  will 
pass  from  the  window  through  the  pin-hole  in  the  card, 
through  the  pupil  and  back  on  to  the  retina.  Since  the  pin- 
hole is  being  constantly  moved  in  a  circle  this  ray  of  light 
will  also  be  continually  traveling  round  and  round  in  a 
circle  over  the  region  of  the  fovea  in  the  retina.  This  is  a 
very  unusual  manner  for  light  to  enter  the  eye.  As  a  result 
the  blood  vessels  which  are  located  in  the  anterior  layers  of 
the  retina  cast  back  their  shadows  on  to  the  rods  and  cones 
in  the  posterior  layers  of  the  retina  in  such  an  unusual  man- 
ner that  these  shadows  are  recognized  by  the  subject.  Their 
form  and  general  distribution  can  be  easily  made  out.  It 
usually  takes  a  long  time  for  a  student  to  learn  to  recognize 
these  shadows  correctly.  He  should  focus  his  eyes  for  a 
long  distance  and  keep  moving  the  pin-hole  round  and 
round  as  he  gazes  through  it  up  into  the  clear  sky.  The 
vessels,  when  finally  recognized,  will  appear  very  much  like 
the  leafless  tops  of  a  number  of  trees  ranged  in  a  circle  in 
such  a  manner  that  the  tops  all  point  toward  the  center  but 
do  not  quite  reach  it,  so  that  a  small  clear  space  is  left  en- 
tirely free  from  vessels  in  the  center.  This  clear  space  cor- 
responds to  the  macula  lutea  or  yellow  spot.  What  do  you 
know  about  this  area? 


'  ACTION    OF    AMYL    NITRITE  403 

When  the  subject  has  learned  to  recognize  clearly  the 
size  and  appearance  of  these  retinal  vessel  shadows  he  may 
determine  the  action  of  amyl  nitrite  on  them.  He  should 
sit  (or  lie)  at  perfect  ease,  and  his  right  hand  should  be 
free  to  keep  up  the  circular  movement  of  the  card.  While 
the  card  is  moving  and  the  vessels  are  being  closely  ob- 
served an  amyl  nitrite  pearl  is  broken  near  the  subject's 
nose  and  the  vapors  are  rapidly  inhaled.  The  subject 
watches  carefully  for  any  change  in  the  size  or  distribu- 
tion (extension  toward  the  macula  or  withdrawal  there- 
from) of  the  retinal  vessel.  How  may  amyl  nitrite  affect 
these  vessels?    Explain  in  detail. 

EXPERIMENT  CXXII. 
Amyl  Nitrite.    (Student:    Effect  on  Vision.) 

1.  On  the  white,  glazed  surface  of  a  sheet  of  drum  paper 
make  a  circular  spot  one-fourth  inch  in  diameter  with  black 
India  ink.  Behind  the  drum  paper  place  several  sheets  of 
perfectly  white  writing  paper  (or  a  sheet  of  Avhite  card- 
board) to  give  a  perfectly  Avliite  background  to  the  drum 
paper.  The  subject  now  sits  quietly  and  looks  at  the  black 
spot  while  amyl  nitrite  vapors  are  administered  to  him. 
Around  the  black  spot  the  subject  watches  for  rings  of  dif- 
ferent colors  to  appear.  If  these  are  observed  how  many 
are  there,  what  is  their  arrangement,  and  what  colors  are 
seen?  How  long  do  they  last?  How  does  amyl  nitrite  act 
to  produce  this  effect  ?  What  is  the  embryological  origin  of 
the  retina? 

If  time  permits  it  will  be  instructive  to  make  a  white  spot 
on  a  black  background  and  repeat  the  experiment  by  inhal- 
ing amyl  nitrite  vapors  Avhile  looking  intentl}^  at  the  white 
spot.  Do  you  know  of  any  other  drugs  which  will  affect 
color  vision?  On  what  nervous  structures  may  such  drugs 
act?  What  relation  does  the  retina  l)ear  to  the  cerebral 
cortex  ? 


404  EXPERIMEiSTTAL   PHARMACOLOGY 

EXPERIMENT  CXXIII. 

Amyl  Nitrite,  Nitroglycerine,  Sodium  Nitrite.     (Dog: 

Blood-pressure,  Respiration,  Spleen  or  Intestinal 

Loop  Volume,  Blood.) 

1.  Prepare  a  dog  for  recording  blood-pressure,  respira- 
tion and  the  volume  of  either  the  spleen  or  a  small  loop  of 
the  intestine.  The  injecting  burettes  contain  nitroglycerine 
(one-fourth  per  cent — the  U.  S.  P.  form  is  one  per  cent) 
and  sodium  nitrite  (one  per  cent).  Place  a  straight  cannula 
in  one  femoral  artery  pointing  toward  the  heart.  Into  a 
test  tube  draw  off  through  this  cannula  five  cubic  centi- 
meters of  blood  and  add  to  the  blood  two  cubic  centimeters 
of  two  per  cent  sodium  chloride  solution.  Set  the  tube 
aside  and  draw  off  five  more  cubic  centimeters  of  blood  into 
a  second  test  tube.  Add  to  this  tube  two  cubic  centimeters 
of  two  per  cent  sodium  nitrite  solution.  Shake  up  both 
tubes  and  let  them  stand  for  some  time.  Do  you  note  any 
changes  in  either  one?  If  so  what  and  how  marked  is  the 
change?  If  a  spectroscope  is  available  a  one-half  or  one 
per  cent  solution  of  each  may  be  made  and  compared  as 
regards  their  spectra  after  the  remainder  of  the  experi- 
ment is  finished. 

Take  a  normal  record  and  prepare  to  give  the  animal 
some  amyl  nitrite.  Proceed  with  this  as  follows :  Keep  the 
anesthesia  as  regular  as  possible.  Open  the  side  tube  of 
the  tracheal  cannula  and  let  the  animal  breathe  mainly 
through  this.  Place  a  pearl  on  a  towel  and  seize  the  pearl 
with  a  pair  of  forceps  through  the  towel  from  below.  In- 
vert the  towel  so  as  to  form  a  ver}^  small  tent-like  chamber 
over  the  end  of  the  side  tube  of  the  tracheal  cannula.  Be 
sure  glass  particles  do  not  fly  into  the  wind  pipe.  When  all 
is  ready  (a  good  normal  record  is  being  taken)  snap  the 
pearl  and  let  the  animal  breathe  the  vapors.  The  effect 
should  come  on  promptly.    It  will  not  last  long  and  after 


ACTION    OF    jSriTEITES 


405 


the  animal  fully  recovers  another  set  of  records  may  l)e 
taken  hj  administering  a  second  pearl.  (Under  special  con- 
ditions yon  may  sometimes  want  to  administer  amyl  nitrite 
to  the  animal  by  placing  the  drug  in  an  empty  ether  bottle 
through  which  the  animal  is  allowed  to  breathe  tem- 
porarily.)   Do  you  note  any  effects  on  the  spleen  or  looj)  of 


.0^  .Cay^-^ytCoL 


Fig.    329. — Tracing  showing  the   action   of  nitroglycerine   on   the   carotid   pressure   and   the 

respiration  in  a  dog. 


intestine?  If  so  how  do  you  account  for  the  action?  Is  it 
an  active  or  a  passive  affair  ?  AVhat  mechanical  factors  are 
involved  ?  Explain  ^\\j  changes  observed  in  the  blood-pres- 
sure and  resjDiration. 

When  the  animal  fully  recovers  take  a  normal  record 
and  then  inject  two  cubic  centimeters  of  the  nitroglycerine 
solution.    Do  you  get  a  satisfactory  record?     (If  not  a  sec- 


406  EXPERIMENTAL   PHARMACOLOGY 

ond  dose  may  be  given  later.)  Explain  your  results  in  de- 
tail. 

Let  the  animal  recover,  take  a  normal  and  then  inject  one 
cubic  centimeter  of  sodium  nitrite  solution.  Do  you  get  a 
satisfactory  record!  (If  not  a  second  dose  may  be  given 
later.)  Explain  your  results  in  detail.  For  what  purpose 
do  you  infer  nitrites  might  be  used  clinically? 

If  the  animal  is  now  in  poor  condition  kill  it  with  a  large 
dose  of  nitrite.  How  much  is  required?  But  if  the  animal 
is  in  fair  or  good  condition  (as  it  probably  will  be)  then  al- 
low it  to  recover  as  fully  as  possible  and  proceed  to  per- 
form the  next  experiment  on  it. 

EXPERIMENT  CXXIV. 

Nitrites,  Pilocarpine,  Adrenaline.    (Dog:    Bronchial 

Action.) 

1.  Arrange  to  record  bronchial  contractions  by  one  of  the 
methods  previously  given.  (If  the  animal  from  Experi- 
ment CXXIII  is  used  remove  the  spleen  or  intestinal  onco- 
meter and  close  the  abdomen  tightly.)  The  injecting  bu- 
rettes contain  one  per  cent  nitrogh^cerine,  pilocarpine  (one 
cubic  centimeter  equals  one  milligram)  and  adrenaline  (1: 
10,000). 

Pith  the  animal,  adjust  the  recording  instruments  and 
take  a  short  normal  record.  Inject  one  cubic  centimeter  of 
pilocarpine.  This  should  produce  a  bronchoconstriction 
which  will  last  for  several  minutes  if  no  other  drugs  are 
given.  When  the  bronchoconstriction  becomes  marked 
then  inject  two  cubic  centimeters  of  nitroglycerine  solution. 
What  action  has  this  on  the  bronchioles?  Would  you  ad- 
vise nitrites  for  bronchial  asthma?  Give  one-half  cubic 
centimeter  of  adrenaline. 

If  the  animal  is  still  in  suitable  condition  a  further  in- 
jection of  pilocarpine   (to  produce  an  initial  bronchocon- 


ACTIOX    OF    DIGITOXIN  407 

striction)  may  be  given  and  this  can  he  followed  hj  an  in- 
jection of  sodium  nitrite  to  determine  the  action  of  this 
body  on  the  bronchial  musculature.  This  is  a  point  of  con- 
siderable clinical  interest.  How  does  adrenaline  compare 
with  the  nitrites  as  regards  its  power  to  dilate  the  bron- 
chioles! Would  it  make  any  difference  whether  the  bron- 
choconstriction  was  due  to  nervous  origin  (as  is  the  case 
with  pilocarpine)  or  to  a  direct  muscular  stimulation  (as 
occurs  with  ergamine)  ?  Which  of  these  conditions  exists 
in  clinical  bronchial  asthma?  Stop  the  artificial  respira- 
tion and  kill  the  animal. 

After  the  animal  is  dead  open  the  chest,  dissect  out  the 
heart  and  study  carefully  the  position  and  relations  of  both 
auricles  and  both  ventricles.  Inflate  the  lungs  and  see  how 
much  these  would  be  in  the  way  in  taking  myocardiograms. 

EXPERIMENT  CXXV. 
Digitoxin.     (Frog:    General  Action.) 

1.  Destroy  the  cerebrum  only  of  a  frog  and  inject  one 
cubic  centimeter  of  digitoxin  solution  (one  cubic  centimeter 
equals  one  milligram — dissolve  the  digitoxin  in  a  few  drops 
of  alcohol  and  then  dilute  with  water,  adding  more  alcohol 
if  necessary  to  prevent  precipitation  of  the  drug.  Use  as 
little  alcohol  as  possible.)  Put  the  frog  in  a  quiet  place  and 
see  if  any  generalized  s3miptoms  appear.  Does  it  have  con- 
\u.ilsions?  If  the  frog  dies  at  any  time  immediately  cut 
open  the  chest  and  observe  carefully  the  condition  of  the 
heart.  Has  it  just  stopped  beating  or  is  it  still  pulsating? 
Digitalis  solutions  are  often  standardized  by  giving  just  a 
sufficient  dose  of  the  preparation  to  stop  the  heart  of  a  frog 
in  one  hour.  This  dose  of  the  standard  solution  is  taken  as 
a  basis,  by  comparison  with  Avhich  newly  prepared  solu- 
tions are  standardized.  Examine  carefully  the  condition  of 
the  ventricle  and  of  the  auricles.  Are  these  chambers  in  sys- 
tole or  diastole?    How  do  you  account  for  the  condition? 


408  EXPERIMENTAL   PHARMACOLOGY 

EXPERIMENT  CXXVI. 
Digitoxin.     (Frog:     Heart  Tracing.) 

1.  Pith  a  frog  and  take  a  normal  heart  tracing  showing 
both  vagns  and  crescent  inhibition.  Then  drop  onto  the 
heart  slowly  a  solntion  of  digitoxin  (five  cubic  centimeters 
equal  one  milligram — dissolve  the  drug  in  a  little  alcohol 
and  dilute  to  the  desired  strength,  adding  more  alcohol  if 
absolutely  necessary.) 

After  the  drug  has  acted  for  a  little  time  stimulate  the 
vagus  nerve  and  see  if  the  inhibitory  apparatus  is  paral- 
yzed. How  is  the  tone  of  the  heart  affected?  Is  this  a 
nervous  or  a  muscular  action?  Continue  the  application  of 
the  drug  and  record  the  entire  action  on  the  heart.  When 
this  heart  stops  compare  its  condition  with  that  of  the  heart 
of  the  frog  used  in  the  preceding  experiment.  A'\Tiat  con- 
clusions can  you  draw? 

EXPERIMENT    CXXVII. 

Digitoxin.     (Turtle:    Heart  Tracing.) 

1.  Repeat  Experiment  CXXVI  using  the  turtle's  heart 
instead  of  that  of  the  frog.  Is  the  inhibitory  apparatus  af- 
fected? 

EXPERIMENT  CXXVIII. 

Digitoxin.    (Dog  or  Cat:    Blood-pressure  and  Respiration.) 

1.  Etherize  a  dog  or  cat  and  take  a  normal  record  of 
blood-pressure  and  respiration.  The  injecting  burette  con- 
tains digitoxin  solution  (ten  cubic  centimeters  equal  one 
milligram — dissolve  the  drug  in  alcohol  and  dilute  with 
water  to  the  proper  strength,  adding  more  alcohol  if  abso- 
lutely necessary).  When  the  normal  is  recorded  (be  sure 
the  manometer  pointer  can  pass  just  to  the  right  of  the  re- 


ACTION    OF    DIGITOXIN 


409 


spiratory  tambour)  inject  sloAvly  and  cautiously  one-hall" 
cubic  centimeter  of  the  drug. 

Caution :  Digitoxin  preparations  on  the  market  are  exceedingly  variable  in 
strength  and  composition.  Each  preparation  must  be  tested  before  the  size 
of  the  dose  for  an  animal  can  be  determined.  The  object  here  is  to  give  very 
small  doses  and  bring  on  the  action  of  the  drug  very  slowly. 


Sl-CoAa^^ 


\m!^\m\\\m\m\\\m\mM^{mm\\ 


Fig.   330. — Tracing  showing  the  action  of  one  milligram  of  digitoxin   on  the  blood-pressure 
and  respiration  in  a  dog.      Slow  drum. 

AVatch  for  any  slight  changes  in  the  amplitude  of  the 
manometer  tracing.  The  drug  should  first  slow  the  heart 
slightly.  The  pressure  may  be  somewhat  elevated  during 
this  period  which  corresponds  to  the  therapeutic  (1st) 
stage.  As  the  action  of  the  drug  becomes  more  marked  the 
heart  is  greatly  slowed  (2nd  stage)  provided  the  inhibitory 
apparatus  is  Avorking  normally.  The  center  is  stimulated 
by  the  drug  and  this  indirectly  slows  the  heart  by  inhilntion. 
Give  a  few  small  injections  slowly  from  time  to  time  at  first 


410 


EXPERIMENTAL   PHARMACOLOGY 


CO 
•n  C 


°'^ 


2-a 


actiojST  of  digitoxin 


411 


to  avoid  killing  the  animal  too  quickly  (some  preparations 
are  exceedingly  poisonous).  As  soon  as  you  determine  the 
tolerance  of  the  animal  to  the  solution  make  larger  and 
more  frequent  injections,  watching  carefully  for  the  marked 


jAaiiiiiiar 


.&;u 


JS^^. 


i«.«.  J9,i^ct6^^^ 


AiAfttlMAiiiiililllTiiiiiiiiiliiiiiiiil 


c/'-cJ^-e-o-***^.  c/^ 


Fig.  332. — Tracing  showing  the  blood-pressure  and  respiration  of  a  dog  under  the 
iniluence  of  di.gitoxin  at  the  time  when  the  second  stage  passed  over  into  the  third  stage. 
Several  small  doses  of  the  drug  were  given  from  time  to  time  to  bring  on  this  action. 


slowing  of  the  second  stage  to  appear.  AYhen  once  you  see 
clearly  that  this  slow  stage  is  beginning  then  stop  all  in- 
jections and  wait  for  the  drug  to  act.  There  Avill  then  prob- 
ably be  sufficient  drug  in  the  animal  to  cause  death  and  it 


412 


EXPERIMENTAL   PHARMACOLOGY 


ACTION    OF    DIGITOXIN 


413 


■5  rt 


414  EXPERIMENTAL   PHARMACOLOGY 

is  desirable  to  prolong  the  later  stages  as  much  as  possible 
to  bring  out  the  action  of  the  drug  well. 

When  marked  slowing  is  present  (vagus  center  stimu- 
lated) the  blood-pressure  may  be  considerably  loAvered. 
After  a  time  irregular  heart  beats  appear  and  the  elevation 
of  the  pressure  varies  from  moment  to  moment.  Watch 
carefully  now,  for  great  irregularity  of  the  heart  ma}^  sud- 
denly appear  at  any  time,  i.e.,  the  vagus  may  lose  control 
of  the  heart  whose  muscle  fibers  become  so  irritable  that 
the  organ  breaks  loose  from  the  inhibition  and  begins  to 
beat  very  rapidly,  and  irregularities,  extra  systoles,  etc., 
soon  appear.  When  this  very  rapid  (3rd)  stage  appears 
the  pressure  may  continue  high  for  a  little  while  but  de- 
lirium cordis  (fibrillation)  is  likely  to  appear  at  any  mo- 
ment. When  it  does  the  pressure  will  fall  to  zero  at  once, 
perhaps  from  a  considerable  height.  The  respiration  will 
stop  at  about  the  same  time  as  a  rule.  Watch  carefully  for 
the  animal  to  die,  and  as  soon  as  the  pressure  suddenly 
falls  to  zero  {and  remains  there)  open  the  chest  quickly 
with  large  tinner's  snips  and  observe  the  condition  of  the 
heart.  It  should  be  fibrillating.  Are  the  chambers  in  sys- 
tole or  diastole.  Place  your  hand  on  the  heart  and  note  the 
character  of  the  movements.  How  long  does  the  fibrilla- 
tion last?  Can  you  determine  the  three  stages  of  the  drug's 
action  on  the  heart  as  shown  by  3^our  record?  What  con- 
clusions can  you  draw  from  the  experiment?  How  much 
drug  is  required  to  kill  the  animal?  Could  you  assay  the 
strength  of  an  unknown  preparation  of  digitalis  by  compar- 
ing the  size  of  the  lethal  dose  of  the  preparation  with  the 
size  of  the  fatal  dose  of  a  standardized  preparation?  On 
this  basis  a  number  of  methods  for  assaying  the  strength 
of  preparations  of  digitalis  and  related  bodies  have  been 
proposed.  (For  literature,  see  Houghton,  E.  M. :  The 
Lancet,  1909,  June  19;  Hatcher  and  Brody:  Journal  of 
Pharmacology,  1910,  August,  p.  362 ;  Famulener  and  L^^ons : 
Proceedings  of  the  American  Pharmaceutical  Association,, 


DIGITOXIN,    STEOPHANTHIN,    NITROGLYCERINE  415 

1902,  p.  417;  Vanderkleed  and  Pittenger:  Journal  of  the 
American  Pharmaceutical  Association,  1913,  xi,  p.  558; 
Edmunds:  Hygienic  Laboratory  Bulletin  No.  48;  Hatcher: 
Journal  of  the  American  Medical  Association,  1910,  ii,  p. 
1697 ;  U,  S.  P.  ix,  p.  606 ;  Pittenger  and  Vanderkleed :  Jour- 
nal of  the  American  Pharmaceutical  Association,  1915.) 

EXPERIMENT  CXXIX. 

Digitoxin,  Strophanthin,  Nitroglycerine.    (Dog:  Pulmonary 
Blood-pressure,  Carotid  Pressure.) 

1.  Arrange  a  dog  for  recording  carotid  and  pulmonary 
blood-pressure  tracings  according  to  the  method  learned 
previously.  Place  cligitoxin  solution  (five  cubic  centimeters 
equal  one  milligram)  in  one  injecting  burette  and  strophan- 
thin solution  (five  cubic  centimeters  equal  one  milligram) 
in  the  other. 

When  all  adjustments  are  ready  take  a  short  normal  rec- 
ord and  inject  one  cubic  centimeter  of  digitoxin.  Wait  for 
the  animal  to  recover.  When  the  records  return  approxi- 
mately to  normal  inject  one  cubic  centimeter  of  strophan- 
thin. Do  you  get  satisfactory  records  from  both  drugs? 
How  is  the  pulmonary  blood  pressure  affected  f  Does  this 
correspond  with  the  systemic  circulation?  Do  the  two 
drugs  act  alike  on  the  pulmonary  vessels!  Which  is  the 
more  powerful?  If  these  doses  were  too  small  to  produce 
any  noticeable  result  give  another  larger  injection  of  each 
one  to  secure  satisfactory  tracings. 

Now  empty  the  digitoxin  out  and  fill  the  burette  (or,  bet- 
ter, connect  a  third  burette  to  a  neck  vein  at  the  start)  with 
one-half  per  cent  nitroglycerine.  Take  a  normal  quickly 
and  then  inject  one  cubic  centimeter  of  the  nitroglycerine 
solution.  Do  you  get  a  satisfactory  record!  If  so  how  is 
the  pulmonary  pressure  affected?  Does  this  have  any 
special  clinical  significance?  How  does  it  compare  witli 
digitoxin? 


416 


EXPERIMENTAL   PHARMACOLOGY 


Eeplace  the  digitoxin  in  the  burette  and  continue  the  re- 
cords. Inject  more  digitoxin  and  strophanthin  from  time 
to  time  and  slowly  bring  on  the  action  of  the  drugs.  Watch 
that  the  animal  does  not  die  suddenly  from  some  unknown 
cause  and  the  drugs  be  accepted  as  the  cause  of  death.    Ani- 


Detail  of 
rubber  baqs 


Glass  tube 


Bdnd  to  attach  bowls  to  lobe  of  liver 


Tube  to 
( tambour 


li 


Ha  I  feck. 


Fig.  335. — Schematic  illustration  showing  the  principles  involved  in  the  construction 
of  Edmunds'  liver  oncometer.  The  two  curved  spoon-shaped  pieces  are  made  of  dental 
impression  compound.  This  is  a  brownish  substance  (resembling  sealing-wax)  which  softens 
and  becomes  easily  moulded  with  the  hands  when  placed  in  hot  water  for  a  while,  but 
hardens  on  cooling.  Obtainable  from  dental  supply  houses.  Thin  flat  rubber  bags  fit 
inside  the  curved  pieces  and  these  bags  tit  just  over  the  outside  of  the  left  lobe  of  the 
exposed  liver.     Records  are  made  by  air  transmission  to   a  tambour. 


mals  arranged  for  recording  pulmonarj''  blood-pressure 
often  do  not  live  long  and  it  is  important  to  work  rapidly 
and  accurately.  Can  you  detect  any  evidence  that  the  heart 
has  been  especially  stimulated  or  strengthened  by  the 
drugs !    Do  you  know  of  any  other  drugs  previously  studied 


DIGITOXIN    AND    STROPHANTHIN 


417 


that  resemble  the  effects  of  digitalis  in  certain  features  of 
their  action? 

Crowd  on  enough  digitoxin  or  strophanthin  to  kill  the 
animal  after  a  few  minutes.    If  you  detect  the  marked  slow- 


iiiiii 

1 

! 

/ 

X 

/-J0,OOO 

mill'*''* 

^a^:-7S^aU.Stl^.       . 

iff  iinmiiiTmTilmiiMiiiiiffiiiff^^ 

mill 

1 

Fig.   336. — Tracina;  shewing   the   action   of  adrenal  ne    on   the   volume   of   the   left  lobe 
of  the  liver  and  on  the  blood-pressure.      Made  with  the  apparatus  shown  in  Fig.   338. 

ing  of  the  heart  indicative  of  the  second  stage  then  stop 
giving  drugs  and  wait  for  the  full  effects  of  the  substances 
to  develop.  Do  you  get  the  third  stage  of  great  irregular- 
ity followed  b}^  delirium  cordis  and  death? 


418  EXPERIMENTAL   PHARMACOLOGY 

After  a  time  kill  the  animal  with  a  large  dose  of  one  of 
the  drugs  if  it  has  not  already  died  as  indicated  above. 
Watch  the  heart  closely  throughout  the  experiment  and  see 
if  you  can  follow  the  changes  occurring  in  the  auricles  and 
ventricles.  If  delirium  cordis  sets  in  which  chambers  are 
affected  by  it  first?  Is  this  of  any  clinical  significance? 
Can  you  detect  this  on  the  carotid  record?  Would  this 
signify  anything  of  importance  from  a  clinical  standpoint? 
Are  the  vagus  endings  in  the  heart  paralyzed  during  the 
third  stage?  Could  you  determine  this  point  during  your 
experiment  in  any  way? 

EXPERIMENT  CXXX. 
Dig-itoxin.    (Dog:    Heart  Tracings,  Carotid  Pressure.) 

1.  Arrange  a  dog  for  recording  tracings  from  both  auri- 
cle and  ventricle  as  was  done  in  previous  experiments.  If 
simple  heart  levers  are  used  the  right  auricle  and  right  ven- 
tricle will  probabl}^  be  the  easier  for  the  student  record.  If 
a  Cushny  myocardiograph  is  available  the  left  ventricle 
can  very  well  be  used.  If  only  one  chamber  can  be  recorded 
then  the  left  ventricle  is  preferred. 

The  records  should  be  arranged  with  the  auricular  tracing 
at  the  top  of  the  drum,  below  this  the  ventricular  tracing, 
then  the  carotid  pressure,  and  finally  the  base  line  (show- 
ing the  time  also).  The  injecting  burette  contains  digitoxin 
(five  cubic  centimeters  equal  one  milligram). 

When  all  adjustments  are  made  take  a  normal  record  and 
begin  to  inject  digitoxin  in  very  small  repeated  doses,  wait- 
ing a  little  while  between  each  dose  to  see  what  its  effect 
will  be.  The  object  now  is  to  bring  on  the  action  of  the 
drug  slowl}^  and  to  watch  to  record  the  changes  in  each 
chamber  as  the  three  stages  develop.  When  the  marked 
slowing  of  the  second  stage  first  begins  to  appear  (due  to 
stimulation  of  the  inhibitory  center  in  the  medulla)  Avatch 
carefully  to  see  whether  the  auricles    or    ventricles    first 


ACTIOj!^    of    DIGITOXIN  419 

sliow  the  retardation.  Do  the  two  auricles  beat  in  alternate 
rhythms  or  synchronously  I  Does  this  hold  true  for  the 
ventricles  also?  Stimulate  one  vagus  nerve  from  time  to 
time  (do  not  injure  the  nerve  by  drying,  etc.,  or  by  too 
strong  a  current)  and  see  if  its  connections  with  the  heart 
muscle  are  destroyed  at  any  time.  Inject  more  drug  from 
time  to  time  until  the  second  stage  is  well  developed.  AVait 
then  and  do  not  give  any  more  drug  unless  it  appears  to  be 
absolutely  necessary  to  bring  on  the  last  stages. 

When  the  stage  of  irregularity  appears  (third  stage)  ob- 
serve carefully  Avhich  chambers  of  the  heart  first  take  up 
the  rapid  rhythm.  Is  this  due  to  paralysis  of  the  vagus 
endings  1 

CavMon:  Sometimes  the  second  stage  of  marked  slowing  is  not  developed 
in  the  heart  (inhibitory  mechanism  weakened  or  paralyzed)  and  the  pulsations 
take  on  a  rapid  character  early  in  the  intoxication  and  the  stage  of  irregularity 
may  follow  after  a  brief  interval.  Slow  administration  of  the  drug  at  tirst  is 
best  calculated  to  bring  on  the  stage  of  marked  inhibition. 

When  the  heart  becomes  very  irregular  observe  the  cor- 
responding changes  in  pressure.  Watch  for  the  sudden  de- 
velopment of  delirium  cordis  (fibrillation)  and  note  which 
chambers  first  show  this  phenomenon.  Do  the  other  cham- 
bers begin  fibrillating  at  once  or  only  after  a  considerable 
interval!  How  does  delirium  cordis  affect  the  blood-pres- 
sure? What  can  you  say  about  delirium  cordis  in  the  frog 
or  turtle? 

Do  you  get  satisfactory  tracings  from  the  heart  showing 
all  the  stages  of  the  poisoning!  Do  you  believe  it  would  be 
possible  to  standardize  digitalis  preparations  according  to 
the  amount  of  the  drug  necessary  to  bring  on  the  different 
stages  in  the  heart  action !  On  what  do  you  base  your  con- 
clusions! What  is  the  cause  of  death  in  digitoxin  poison- 
ing! The  administration  of  the  drug  should  be  continued 
(at  long  intervals)  until  the  animal  dies — which  will  prob- 
ably be  rather  suddenly.  Judging  from  your  experiment 
what  should  be  the  clinical  symptoms  of  the  first  or  thera- 


420  EXPERIMENTAL   PHARMACOLOGY 

peutic  stage  of  the  action  of  digitoxini    Discuss  the  action 
of  the  drug  on  the  heart  in  detail. 


'■t) 


EXPERIMENT  CXXXI. 

Digitoxin,  Strophanthin.    (Dog:    Diuresis,  Spleen  Volume, 
Leg  Volume,  Blood-pressure  and  Respiration.) 

1.  Arrange  a  dog  for  recording  hlood-iDressure  and  leg 
volume.  Then  open  the  abdomen  and  isolate  both  ureters 
near  the  bladder.  Place  a  cannula  in  each  ureter  and  ar- 
range to  collect  the  urine  secreted.  Now  place  the  spleen 
in  an  oncometer  and  arrange  to  record  the  volume  changes 
of  the  organ.  On  the  drum  the  s^Dleen  volume  should  be  at 
the  top,  next  below  the  leg  volume,  then  the  blood-pressure 
and  respiration  with  the  time  marked  on  the  base  line.  The 
Tate  of  urine  flow  may  be  recorded  mth  a  signal  magnet  by 
a  hand  key  and  dry  cell  if  desired.  The  injecting  burettes 
■contain  digitoxin  (ten  cubic  centimeters  equal  one  milli- 
gram) and  strophanthin  (ten  cubic  centimeters  equal  one 
milligram). 

When  all  is  ready  wait  a  while  to  get  a  record  of  the  nor- 
mal rate  of  urine  secretion.  Then  take  a  normal  record  and 
inject  one  cubic  centimeter  of  digitoxin  solution.  Is  the 
dose  too  small?  Give  one  cubic  centimeter  of  strophanthin. 
Which  affects  the  animal  the  most?  Inject  a  few  more 
doses  very  cautiously  and  then  wait  for  some  time  to  see  if 
the  rate  of  urine  flow  is  changed.  If  it  is  how  does  this  com- 
pare with  the  action  of  caffeine  or  sodium  sulphate? 

After  time  has  been  given  for  an  action  on  the  kidney  to 
develop  (is  this  certain  to  occur?)  then  adjust  all  writing 
points  and  take  a  normal.  Then  inject  a  good  sized  dose  of 
digitoxin  as  estimated  from  your  previous  experience  with 
the  drug  and  with  the  animal.  How  does  this  affect  the 
spleen  and  leg?  Do  the  other  records  show  a  correspond- 
ing action?.  Wait  a  while  and  give  a  similar  injection  of 
strophanthin.    How  does  the  action  of  this  drug  compare 


SPLEEN    ONCOMETER 


421 


3Tiap     / 


Noich  for 
Meseni-erv  of 
Spleen. 


Fig.  337. — Spleen  oncometer  made  of  crimped  sheet  brass  soldered  together.     Nearly  natural 

size.      (For  a  dog.) 


422 


EXPERIMENTAL   PHARMACOLOGY 


with  the  cligitoxin?  Are  the  vessels  of  the  internal  organs 
and  of  the  leg  both  affected  in  the  same  Avay  and  in  corre- 
sponding degrees  by  these  two    drugs?      (See    Edmunds: 


Fig.  338. — Liver  oncometer,  for  the  left  lobe  of  the  liver  of  a  dog.  Made  of  crimped 
sheet  brass.  The  lid  (raised  up)  is  slipped  under  the  lobe  and  the  cup-like  part  closes 
over  the  lobe  to  inclose  it.  The  "pedicle"  of  the  lobe  passes  through  the  large  notch  at 
the  right  in  the  picture.  The  spout  is  connected  to  a  tambour  and  the  abdomen  is  closed 
air  tight. 


American  Journal  of  Ph^^-siology,  xviii,  p.  129.)  What  can 
you  say  about  the  action  of  the  digitalis  series  of  drugs  on 
the  medullary  centers  1    ( See  Hatcher  and  Eggieston :  Jour- 


LIVER    VOLUME    CHAjSTGES 


423 


nal  of  Pharmacology  and  Experimental  Therapeutics,  iv, 
p.  113.) 
.  Do  these  large  injections  of  the  drugs  affect  the  kidneys? 


Fig.  339.— Tracing  showing  the  action  of  tetramethylammonium  chloride  on  the  liver 
volume  and  blood-pressure  in  a  dog.  The  respiratory  movements  show  in  the  oncometer 
tracing.     The  animal  was  breathing  deeply.     Made  with  the  oncometer  shown  in   i-ig.   3Jt-. 

In  what  ways  might  they  influence  the  secretion  of  urine? 
When  satisfactory  records  have  been  obtained  inject  a 
large  dose  of  one  of  the  drugs  and  get  a  death  record. 


424  EXPERIMEiSTTAL   PHARMACOLOGY 

Have  you  shown  all  three  stages  of  the  heart  action  in  your 
experiment  1  What  general  conclusions  can  you  draw  from 
the  experiment? 

EXPERIMENT  CXXXII. 

Adrenaline,  Potassium  Chloride,  Digitoxin,  Strophanthin. 
(Cat,  Rabbit,  Dog:     Heart  Perfusion — Langendorff 

Method.) 

1.  Set  up  your  apparatus  with  great  care  in  the  manner 
shown  in  Fig.  340.  Prepare  several  liters  of  stock  salt  solu- 
,tion  (Locke's  preferred).  Place  two  liters  of  the  solution 
in  the  pressure  bottle  and  heat  the  water  bath  to  39  de- 
grees centigrade.  Place  water  in  the  heart  warmer  (a  hot 
water  funnel  may  be  substituted  for  the  cheap  heart  warm- 
er here  shown)  and  heat  the  warmer  to  39  degrees  centi- 
grade. 

When  all  apparatus  is  arranged,  including  the  adjust- 
ment of  the  cannula  (lower  end  of  a  glass  T-tube  with  a 
neck  drawn  on  it)  for  insertion  into  the  aorta,  then  etherize 
the  animal  and  connect  a  burette  to  one  femoral  vein.  A 
straight  cannula  is  placed  in  one  carotid  pointing  toward 
the  heart  to  bleed  the  animal.  Draw  off  as  much  blood  as 
will  flow  readily  out  of  the  carotid  and  whip  this  until  the 
fibrin  is  all  removed.  Meanwhile  siphon  off  a  liter  and  a 
half  of  the  warmed  salt  solution  from  the  pressure  bottle 
and  inject  a  liter  or  more  of  the  warm  solution  into  the 
femoral  vein.  This  will  revive  the  animal  somewhat  and  it 
may  then  be  bled  further  from  the  carotid.  All  the  blood  is 
carefully  saved,  whipped  free  from  clots,  filtered  through 
cloth  or  cotton  and  placed  in  the  pressure  bottle  (which  con- 
tains now  one-half  liter  of  warmed  salt  solution).  This 
mixture  of  whipped  blood  and  salt  solution  forms  the  stock 
perfusion  fluid.  More  salt  solution  can  be  added  to  it  to 
bring  the  volume  up  to  four  or  five  times  its  original 
amount  or  more. 


HEART    PERI'^USIOIS^    APPARATUS 


425 


Funnel  (refilling 
5-  air  vent) 


Stock  solution 
(Diluted  blood -h 
a  salt  solution) 

l^eral  pan 
Hot  water  batti 


Fig.  340. — Arrangement  of  apparatus  for  recording  tracings  from  an  excised  heart 
(Langendorff  method).  The  heart  warmer  is  made  of  two  cheap  metal  pails  held  together 
by  a.  metal  tube  soldered  between  them  at  the  bottom.  Through  this  tube  passes  the  thread 
attached  by  a  pin  hook  to  the  heart.  The  space  between  the  pails  is  filled  with  water 
heated  by  the  flame  of  a  Bunsen  burner  applied  to  the  heating  rod. 


426 


EXPERIMENTAL   PHARMACOLOGY 


lAHien  no  more  blood  can  be  obtained  from  the  animal 
(by  injecting  salt  solution)  then  quickly  open  the  chest  by  a 
median  incision  with  tinner's  snips  and  carefully  excise  the 
heart  and  lungs.  Do  not  injure  the  vessels  or  tissues  of  the 
heart  and  Avatch  that  the  auricles  are  not  cut  away.  The 
aorta  should  be  left  an  inch  or  more  long.  Cut  off  the  lungs 
and  free  the  heart  as  much  as  possible  from  fascia  but  do 
not  tear  the  vessels.  Tie  all  the  large  branches  of  the  aorta, 
slip  the  main  aortic  trunk  over  the  perfusion  cannula  (do 


R.  Ventricle 


H./\urjcle 
Precava 


Brachiocephalic  Art. 
R.Subdavian  Art. 

R.CarotidM 


Postcava 


L.ventricle 


jj^/^a/f. 


LAurJcie 
Pulmonary  vein 


LCarotid  Art 

L.SubclavlanArt 
Aorta 

Ductus  arteriosus 
Pultnonary  Art 


Fig.    341. — Cat's   heart. 


not  insert  the  cannula  far  enough  to  interfere  with  the 
semilunar  valves  or  the  coronary  arteries)  and  tie  the  can- 
nula in.  Let  the  air  all  out  of  the  perfusion  tubes  (by  open- 
ing the  outlet  and  running  doAvn  some  of  the  perfusion  fluid 
while  the  aorta  just  below  the  cannula  is  closed  by  a  bull- 
dog). Remove  the  bull-dog  and  start  the  perfusion.  Oxy- 
gen should  be  started  to  bubbling  slowly  through  the  stock 
solution.  (Compressed  air  may  be  used  instead  of  oxygen.) 
The  temperature  of  the  perfusion  solution  should  be  kept  at 
about  39  degrees  centigrade.  The  heart  may  not  beat  at 
first,  but  after  a  time  the  beats  will  begin  and  soon  become 


PERFUSION    OF    THE    HEART 


427 


strong  and  vigorous.  Then  take  a  normal  record.  Return 
the  fluid  which  has  already  passed  through  the  heart  to  the 
stock  solution  and  prepare  to  inject  some  adrenaline  with 
the  hypodermic  syringe  through  the  wall  of  the  rubber  tube 
just  above  the  heart.  Two  cubic  centimeters  of  1:10,000 
solution  may  be  injected  slowly  and  steadily.  How  does 
this  affect  the  record?  How  long  does  the  action  on  the 
heart  last!    Do  not  return  the  solution  into  ivliich  any  drug 


Apex 


Vessels  ^  faf  in  left  or  ventral 
~^  loncjituclinal  qroove 


^Ricjhf  ventricle 


Lef-t  veniricle 
Left  auricle  — 


Posterior 
vena  cava 


Pulmonary  Veins 


Conus  arteriosus 

Pulmonary  Artery 

Riqht  auricle 
Anterior  vena  cava 


Brachio- 
cephalic Art. 


Left  Brachial  Artery 
Li(famentum  arteriosum 


Left  Pulmonary  Artery 


Fig.  342.— Dog's  heart. 

has  passed  to  the  stock  solution.    Change  beakers  to  catch 
the  outflow  as  soon  as  the  drug  has  all  passed  out. 

When  the  heart  returns  to  normal  inject  some  potassium 
chloride  solution  (one  per  cent)  and  get  a  record  of  the  re- 
sult. Follow  this  with  a  solution  of  digitoxin  (five  cubic 
centimeters  equal  one  milligram).  Do  not  inject  too  much. 
How  does  this  affect  the  heart?  AYhen  a  satisfactory  record 
has  been  obtained  (give  more  digitoxin  if  necessary)  then 
inject  a  second  dose  of  potassium  chloride  and  follow  this 


428  EXPERIME2TTAL   PHARMACOLOGY 

with  strophantliin  (five  cubic  centimeters  equal  one  milli- 
gram). How  does  this  affect  the  heart  ?  Do  you  get  satis- 
factory records?  If  the  heart  is  in  a  suitable  condition 
other  drugs  which  may  be  tried  are  camphor,  strychnine, 
pilocarpine,  atropine,  adonidin,  calcium  chloride,  caffeine, 
chloroform,  aiDomorphine,  nicotine,  cocaine,  etc.  It  may 
be  advisable  to  kill  the  heart  with  digitoxin.  If  this  is  done 
watch  carefully  to  see  if  delirium  cordis  is  produced  and  if 
so  what  chambers  are  first  aifected.  Also  in  what  part  of 
the  cardiac  cycle  does  the  heart  stop!  Does  it  stop  in 
systole  or  diastole  in  the  intact  animal?  What  explanation 
can  you  offer?  What  general  conclusions  can  you  draw 
from  the  experiment?  What  x)art  do  the  coronary  arteries 
and  veins  play  in  the  experiment?  What  are  the  sinuses  of 
Valsalva?  AVhat  is  their  function?  Will  the  absence  of 
intraventricular  or  intra-auricu]ar  pressure  in  any  way  in- 
validate your  observations? 

There  are  several  other  methods  for  studying  the  action 
of  drugs  on  the  isolated  heart,  e.g.,  those  of  Frank,  Martin, 
Bock,  Starling,  Heymans  and  Kochman,  etc.  (See  Heinz: 
Handbuch  der  Pathologie  und  Pharmakologie,  i,  2,  pp.  669 
and  846  et  seq.;  also  Sollmann:  A  Text-book  of  Pharmacol- 
ogy, 2nd  edition,  1906,  W.  B.  Saunders  Co.,  pp.  895  and  953.) 

EXPERIMENT  CXXXIII. 
Aconitine.     (Frog:     General  Action.) 

1.  Destroy  the  cerebrum  only  of  a  frog,  wait  for  the 
shock  to  wear  off  and  then  inject  one  cubic  centimeter  of 
aconitine  solution  (aconitine  "potent,"  five  cubic  centi- 
meters ec[ual  one  milligram)  into  the  dorsal  lymph  sac. 
Watch  the  symptoms  carefully  and  see  if  there  is  any  stimu- 
lation of  the  central  nervous  system.  Are  the  muscles  af- 
fected?   What  .general  conclusions  can  you  draw? 


ACTION    OF    ACONITIXE  429 

EXPERIMENT  CXXXIV. 
Aconitine.     (Frog:     Heart  Tracing.) 

1.  Determine  tlie  action  of  aconitine  on  the  heart  and  in- 
hibitory apparatus  of  a  frog.  Leave  the  meclidla  intact. 
Inject  the  drug-  into  the  dorsal  lymph  sac  with  a  h^qoodermic 
syringe.  The  action  on  the  heart  is  of  some  s^Decial  interest 
because  of  the  peculiar  behavior  of  the  organ  under  the  ac- 
tion of  the  drug.  This  heart  action  has  been  thought  to  be 
of  some  value  in  identifying  aconitine.  What  can  you  say 
regarding  the  chemical  tests  for  the  identification  of  aconi- 
tine? Do  you  know  of  any  other  drugs  that  act  on  the 
frog's  heart  in  a  manner  similar  to  that  of  aconitine? 

EXPERIMENT  CXXXV. 
Aconitine.    (Turtle:    Heart  Tracing.) 

1.  Repeat  the  above  experiment  using  a  turtle  instead  of 
a  frog.  Apply  the  drug  directly  to  the  heart.  What  gen- 
eral conclusions  can  3^ou  draw? 

EXPERIMENT  CXXXVI. 

Aconitine.    (Dog:    Blood-pressure,  Respiration, 
Temperature.) 

1.  Arrange  to  record  the  blood-joressure,  respiration  and 
temperature  (rectal  thermometer).  After  the  experiment 
starts  make  a  record  of  the  temperature  reading  every 
three  or  five  minutes.  Place  aconitine  solution  (aconitine 
"potent,"  ten  cubic  centimeters  equal  one  milligram)  in 
the  injecting  burette.  Isolate  and  ligate  loosely  [hut  do 
not  injure)  both  vagus  nerves.  When  all  is  ready  take  a 
normal  tracing  and  then  inject  one-half  cubic  centimeter  of 
aconitine  solution.    Some  samples  of  aconitine  are  exceed- 


430  EXPERIMENTAL   PHARMACOLOGY 

ingly  poisonous  and  the  doses  must  at  first  be  small  and 
guarded  or  the  animal  may  be  killed  immediately  and  the 
details  of  the  action  of  the  drug  cannot  be  made  out.  The 
object  now  is  to  give  small,  repeated  injections  and  bring 
on  the  action  of  the  drug  very  sloivly. 

If  everything  is  working  satisfactorily  you  should  ob- 
serve after  a  time  a  slight  slowing  of  the  heart.  This  is 
manifested  by"  a  gradual  increase  in  the  amplitude  of  the 
manometer  tracing.  The  pressure  will  slowly  become  low- 
er. Do  not  crowd  on  the  drug  but  wait  patiently  for  the 
vagus  center  to  be  roused  to  greater  and  greater  activity. 
Meanwhile  the  heart  muscle  is  becoming  slowly  more  and 
more  irritable.  But  if  the  inhibitor}^  apparatus  is  normal 
it  will  at  first  get  the  upper  hand  and  the  heart  should  fi- 
nall}^  be  greatly  slowed.  Is  there  any  way  by  which  you  could 
prove  that  the  heart  slowing  is  due  to  stimulation  of  the 
vagus  center?  Continue  the  injections  very  cautiously  and 
when  the  heart  becomes  noticeably  slower  then  stop  the  in- 
jections and  wait  to  see  if  the  action  of  the  drug  does  not 
become  progressively  more  marked  without  further  injec- 
tions. In  some  experiments  the  heart  may  become  so 
slowed  that  the  manometer  tracing  will  show  an  amplitude 
of  one-half  to  three-fourths  of  an  inch  for  each  separate 
heart  beat.  When  this  stage  is  approached  then  carefully 
lift  up  both  vagus  nerves  and  quickly  cut  them  with  the 
scissors.  What  effect  has  this  on  the  blood-pressure  and 
heart  beat? 

Caution:  Do  not  mistake  the  carotid  artery  and  cut  it  instead  of  one  vagus 
nerve  as  the  author  has  seen  a  student  do.  What  would  you  do  if  this  accident 
occurred  ? 

Wait  a  while  now  and  see  if  the  action  of  the  drug  de- 
velops further  without  giving  any  more  of  the  poison.  How 
does  the  heart  beat?  Can  you  determine  the  true  action  of 
the  heart  by  watching  the  mercury  manometer?  Does  the 
pressure  become  exceedingly  irregular?  It  should  do  so 
and  then  after  a  longer  or  shorter  period  (usually  only  a 


ACTION    OF    ACONITINE  431 

few  iiiiniites)  the  heart  suddenly  goes  into  delirium  cordis 
and  the  pressure  quickly  falls  to  zero.  It  may  be  necessary 
to  give  a  little  more  of  the  drug  to  produce  the  final  effects 
within  a  sufficiently  short  time. 

How  did  section  of  the  vagi  affect  the  respiration!  What 
was  the  very  first  abnormal  action  which  your  animal 
showed  as  seen  in  your  tracing?  Examine  the  respiratory 
record  closely.  What  general  conclusions  can  you  draw? 
If  the  vagi  had  not  been  cut  what  Avould  have  happened  to 
the  heart!  If  two  or  more  experiments  are  performed  at 
the  same  time  one  group  of  students  should  cut  the  vagi,  a 
second  group  should  give  one  milligram  of  atropine  and  a 
third  should  let  the  action  of  the  aconitine  proceed  without 
interfering  in  any  way.  Immediately  after  the  animal  dies 
open  the  chest  quickly  and  see  if  the  heart  is  fibrillating. 

EXPERIMENT  CXXXVII. 

Aconitine.    (Dog:    Heart  Tracing's,  Blood-pressure.) 

1.  As  in  Experiment  CXXX  under  cligitoxin,  arrange  to 
record  blood-pressure  and  heart  tracings  from  a  dog.  Place 
aconitine  solution  (ten  cubic  centimeters  equal  one  milli- 
gram) in  the  burette. 

AVhen  a  normal  record  has  been  taken  then  very  slowly 
and  cautiously  inject  small  repeated  doses  of  aconitine.  The 
object  is  to  bring  on  the  action  very  slowly  and  to  let 
each  phase  of  the  heart  reaction  be  fully  developed.  Watch 
the  chambers  of  the  heart  and  see  which  ones  first  show  ab- 
normalities. Over  what  chambers  of  the  heart  do  the  vagus 
nerves  exercise  the  fullest  control!  Can  you  see  any  evi- 
dence of  this  by  watching  the  heart  as  the  action  of  the 
drug  comes  on? 

Do  you  get  the  stage  of  marked  slowing  as  in  the  previous 
experiment!  Do  the  two  auricles  beat  together  or  in  dif- 
ferent rhythm!    Is  this  true  for  the  ventricles  also !    Does 


432 


EXPERIMENTAL   PHARMACOLOGY 


/o^^A 


rm\ 


Fig.  343. — Tracing  showing  the  final  action  of  aconitine  on  the  heart  (myocardiogram, 
right  auricle  and  right  ventricle)  and  blood-pressure  in  a  dog.  The  contractions  are  very- 
fast  and  irregular. 


ACONITINE    AND    VERATPJNE  433 

this  hold  ill  the  case  of  the  frog?  Watch  for  the  sudden  ap- 
pearance of  irregular  heart  heats,  extra  sj'stoles,  etc.  In 
what  chainbers  are  these  first  developed?  Can  3^ou  get 
satisfactory  records  of  the  heart  movements  when  the  rate 
is  exceedingly  fast?  Watch  for  the  sudden  development 
of  delirium  cordis.  What  happens  to  the  blood-pressure 
■when  this  occurs  ?  After  the  heart  begins  to  fibrillate  stimu- 
late the  vagi  and  see  if  you  can  stop  the  fibrillation.  What 
conclusions  can  you  draw?  Feel  of  the  heart  and  describe 
the  nature  of  the  fibrillary  contractions. 

EXPERIMENT  CXXXVIIT. 

Aconitine.    (Student:    Local  Action.) 

1.  Saturate  a  piece  of  filter  paper  one-fourth  inch  square 
with  a  solution  of  aconitine  (ten  cubic  centimeters  equal  one 
milligram)  and  place  the  filter  paper  on  the  tongue.  Do 
not  swallow  any  of  the  solution.  After  a  little  while  re- 
move the  paper  and  note  the  sensation  produced  on  the 
tongue.  What  conclusions  can  you  draw?  (If  the  solution 
was  too  weak  a  stronger  one  may  be  used.) 

EXPERIMENT  CXXXIX. 

Veratrine.     (Frog:    General  Action.) 

1.  Destroy  the  cerebrum  only  of  a  frog,  wait  for  the  shock 
to  disappear  and  then  inject  one  cubic  centimeter  of  vera- 
trine sulphate  solution  (ten  cubic  centimeters  equal  one 
milligram)  into  the  dorsal  lymph  sac.  Place  the  animal  on 
a  table  and  wait  a  little  while  for  the  drug  to  be  absorbed. 
From  time  to  time  touch  the  animal  gently  and  get  it  to 
jump.  Do  you  notice  anything  unusual  about  its  move- 
ments? Does  it  have  trouble  in  extending  or  relaxing  its 
muscles?  Does  it  have  spontaneous  convulsions?  Examine 
the  skin  to  see  if  there  is  an  increased  cutaneous  secre- 


434  EXPERIMENTAL   PHARMACOLOGY 

tioii.  The  animal  after  a  time  will  be  able  to  jmiip  very  well 
but  will  alight  with  the  hind  legs  extended  and  the  fore  legs 
passed  back  along  the  flanks.  Only  with  difficulty  can  the 
animal  then  draw  up  its  hind  limbs.  What  is  the  cause  of 
this  difficulty!  After  some  time  (if  the  dose  was  large 
enough)  the  animal  becomes  completely  paralyzed  and  dies. 
Then  expose  the  heart  and  note  whether  it  stopped  in 
systole  or  diastole.  In  what  condition  does  the  heart  usu- 
ally stop !  Is  this  true  for  a  mammal  also  ?  What  can  you 
say  of  the  general  action  of  veratrine '? 

EXPERIMENT  CXL. 

Veratrine.    (Frog  or  Turtle:    Heart  and  Inhibitory 
Apparatus.) 

1.  Arrange  a  frog  or  turtle  for  taking  heart  tracings. 
Make  a  normal  record  (showing  both  vagus  trunk  and  cres- 
cent inhibition).  Pour  a  few  drops  of  veratrine  (sulphate 
or  hydrochloride)  solution  (ten  cubic  centimeters  equal  one 
milligram)  on  the  heart  and  record  the  effect.  After  the 
drug  has  acted  a  few  moments  stimulate  the  vagus  nerve 
again  and  see  if  the  heart  is  inhibited.  Also  stimulate  the 
crescent  and  see  what  happens.  What  conclusions  can  you 
draw?  Apply  more  of  the  drug  and  record  the  full  action 
on  the  heart.  Is  there  any  visible  difference  between  the 
action  on  the  ventricle  and  that  on  the  auricles?  Would 
your  method  of  suspension  obscure  the  appearance  of  the 
behavior  of  the  heart  under  the  drug  ? 

EXPERIMENT  CXLI. 

Veratrine.    (Frog:    Skeletal  Muscle.) 

1.  Set  up  your  apparatus  as  shown  in  Experiment  XL VII, 
p.  245  (see  also  Experiment  XCVI  under  cocaine),  for  re- 
cording muscular  contractions.    Then  pith  a  frog  and  ligate 


ACTION    OF    YERATRIXE 


435 


the  left  thigh  tightly.  Under  the  skin  of  the  back  inject  two 
cubic  centimeters  of  veratrine  solution  (five  cubic  centi- 
meters equal  one  milligram)  and  attach  the  animal  to  the 
frog  board  as  illustrated.  Connect  the  secondary  wires  to 
the  tendo  Achillis  and  to  the  carpet  tack.  Do  not  stimulate 
the  muscle  as  the  first  contraction  is  the  one  which  will  in 


^(^^ti^  ^^e.t(le^/t>»«'toi^i''^'T^. 


Fig.  344. — Frog  heart  tracing  showing  the  action  of  veratrine.  The  vagus  trunlc  was 
stimulated  as  indicated.  Inhibition  occurred  before  but  not  after  veratrine  was  applied. 
What   action  did  the  drug  have   here?      How   would  you  prove  your  conclusions? 


all  likelihood  shoAv  the  action  of  the  drug  the  best  and  this 
one  should  be  recorded.  Adjust  the  inductorium  connec- 
tions for  single  shocks  and  use  only  the  hreak  shock  to 
stimulate  the  muscle.  About  ten  or  fifteen  minutes  should 
be  allowed  for  absorption  of  the  drug.  AVhen  everything 
is  entireli)  ready  start  the  drum  (medium  speed)  and  when 


436  EXPEEIMENTAL   PHARMACOLOGY 

the  muscle  lever  has  recorded  a  line  half  an  inch  long  (be 
sure  the  lever  is  properly  weighted  and  adjusted)  stimulate 
the  muscle  with  one  single  shock.  The  muscle  should  con- 
tract quickly  but  the  relaxation  is  much  prolonged  and 
usually  shows  certain  peculiarities.    Let  the  drum  run  and 


Fig.  345. — Arrangement  of  apparatus  for  spinning  tlie  drum  a  single  round  at  a  time 
and  stimulating  a  muscle  or  nerve  with  a  single  shock  during  the  revolution  of  the  drum. 
(See  Jour.  Amer.  Med.  Assoc,  1911,  56,  1705.) 

record  the  full  relaxation  but  as  soon  as  the  lever  again 
reaches  the  base  line  stimulate  the  muscle  again  mth  one 
single  shock.  Eecord  this  contraction  and  when  the  lever 
again  comes  down  to  the  base  line  repeat  the  stimulation. 
A  series  of  contractions  will  thus  be  secured.    The  charac- 


ACTIOi^    01'    YERATPJNE  437 

ter  of  these  contractions  clianges  rapidly  Avitli  eacli  sncceed- 
ing-  curve  until  a  perfectly  normal  record  may  he  secured. 
Exj)lain  the  nature  of  this  change  in  the  contraction  curves. 
AVhy  are  there  undulations  at  the  top  of  the  curves  ?  What 
effect  has  fatigue  on  the  action  of  the  drug  f  Let  the  muscle 
rest  a  while  and  see  if  you  can  get  a  second  series  like  the 
first.  Now  take  a  few  contraction  records  from  the  normal 
(left)  gastrocnemius  muscle  to  compare  with  the  curves 
showing  the  drug  action. 

EXPERIMENT  CXLII. 

Veratrine.     (Turtle:    Lung  Tracing.) 

1.  Arrange  a  turtle  for  recording  lung  tracings.  Inject 
two  cubic  centimeters  of  veratrine  solution  (ten  cubic  centi- 
meters equal  one  milligram)  into  the  ventricle  and  note  the 
action  on  the  lungs.  If  this  does  not  give  3^ou  a  record  then 
pour  some  of  the  solution  over  the  lungs  (local  application). 
Do  you  get  a  record  I  If  so  on  what  structures  did  the  drug 
act  to  produce  the  result?  (It  is  very  acMsable  to  remove 
all  the  intestines,  liver  and  bladder  and  as  much  as  possible 
of  the  skeletal  muscles  from  the  turtle  before  making  a  test 
on  the  lungs,  for  sometimes  the  skeletal  muscles  suddenly 
contract  and  obscure  the  results.  The  cord  should  also  be 
thoroughly  pithed.  One  can  then  look  at  the  lungs  closely 
and  see  if  they  contract.) 

EXPERIMENT  CXLIII. 

Veratrine,  Adrenaline.    (Dog:  Blood-pressure,  Respiration, 
Intestinal  Contraction.) 

1.  Arrange  a  dog  for  recording  blood-pressure,  respira- 
tion and  intestinal  contractions.  The  burettes  contain  verat- 
rine (ten  cubic  centimeters  equal  one  milligram)  and 
adrenaline  (1:10,000). 


438 


EXPERIMENTAL   PHARMACOLOGY 


ACTIOIs^  OF  veratrijs:e  439 

AVlien  all  adjustments  are  made  take  a  normal  and  in- 
ject one  cubic  centimeter  of  veratrine  solution.  Do  you  get 
an  intestinal  record?  The  dose  was  probably  too  small  but 
the  toxicit}^  of  commercial  preparations  varies  greatly  and 
some  samples  are  exceedingly  poisonous.  AVhen  once  you 
have  determined  the  dose  which  your  animal  can  withstand 
then  inject  a  larger  amount  and  watch  for  intestinal  con- 
tractions. (One  group  of  students  should  also  record  the 
bladder  contractions.)  The  respiration  should  be  affected 
rather  earh^  Watch  for  the  heart  to  become  slower.  This 
will  be  seen  in  the  increased  amplitude  of  the  manometer 
tracings. 

The  action  of  the  drug  should  now  be  brought  on  slowly 
as  with  aconitine  and  digitoxin.  This  is  the  best  way  to 
bring  out  the  central  vagal  stimulation  which  slows  the 
heart.  The  beating  of  the  heart  should  finally  become  very 
slow  and  the  amplitude  of  each  beat  as  recorded  by  the 
manometer  may  reach  half  an  inch  or  more  in  length.  If 
you  succeed  in  getting  this  action  then  suddenly  cut  both 
vagus  nerves  and  see  if  the  heart  accelerates  as  after  aconi- 
tine. Does  veratrine  make  the  heart  more  irritable!  Do 
you  get  a  stage  of  irregular  heart  beats  as  occurs  Avith 
aconitine  f  Kill  the  animal  by  repeated  injections  of  the 
drug.  What  general  conclusions  can  you  draw  from  the 
experiment?  If  another  group  of  students  are  performing 
the  experiment  at  the  same  time  then  one  group  can  give 
the  animal  an  injection  of  one  cubic  centimeter  of  atropine 
(one  cubic  centimeter  equals  one  milligram)  instead  of  cut- 
ting the  vagus  nerves.  A  third  group  may  let  the  veratrine 
take  its  regular  course  of  action,  neither  cutting  the  vagi 
nor  giving  atropine.    The  groups  can  compare  their  results. 

Examine  your  respiratory  record  closely  and  see  whether 
any  indications  of  a  Cheyne-Stokes  type  of  lu'eathing  are 
present.  Is  the  respiratory  disturbance  due  to  a  central  or 
a  peripheral  action ! 


440  EXPEEIMENTAL   PHARMACOLOGY 

EXPERIMENT  CXLIV. 
Veratrine.    (Dog:    Heart  Tracings,  Blood-pressure.) 

1.  Record  heart  tracings  from  a  dog  showing  the  action 
of  veratrine.  Proceed  as  in  Experiment  CXXXVII,  p.  431^ 
or  Experiment  CXXX,  p.  418. 

(Cardiometer  tracings,  from  the  ventricles,  may  also  be 
recorded  in  another  animal.) 

EXPERIMENT  CXLV. 
Apomorphine.       (Dog:  Vomiting  Center.) 

1.  Inject  snbcutaneonsly  into  a  dog  (eight  to  ten  kilos) 
one  or  two  cnbic  centimeters  of  apomorphine  hydrochloride 
(one  cnbic  centimeter  eqnals  five  milligrams).  Leave  the 
animal  in  a  cpiiet  place  and  observe  its  actions  from  time  to 
time  for  three  or  fonr  lionrs.  Is  there  any  noticeable  action 
on  the  cerebrnm  or  cerebellnmf  What  general  symptoms 
are  prodnced?  What  conclnsions  can  yon  draw  from  the 
experiment!  Are  the  pnpils  affected!  Is  there  salivation! 
If  so  how  do  you  explain  it! 

EXPERIMENT  CXLVI. 
Ipecac.    (Dog:  Emesis.) 

1.  Administer  by  stomach  to  a  dog  (eight  to  ten  kilos) 
three  cnbic  centimeters  of  the  flnid  extract  of  ipecacuanha. 
Leave  the  animal  in  a  cpiiet  place  and  observe  its  actions 
from  time  to  time  for  three  or  four  hours.  What  general 
symptoms  are  produced!  What  conclusions  can  you  draw 
from  the  experiment!  What  are  the  chief  differences  be- 
tAveen  the  actions  of  apomorphine  and  ipecac! 


ACTION    OF    CYAiSriDi:S  441 


EXPERIMENT  CXLVII. 


Sodium  Cyanide,   (Hydrocyanic  Acid),  Sodium  Sulphide, 
Hydrogen  Peroxide.    (Dog:  Respiration,  Blood-pres- 
sure, Oxygen  Consumption,  Blood,  Glycosuria.) 

1.  Arrange  a  dog  (give  a  small  dose  of  cliloretone)  for 
recording  hlood-pressure,  respiration,  and  oxygen  con- 
sumjDtion.  The  injecting  burettes  contain  either  sodium 
cyanide  (one-half  per  cent)  or  hydrocyanic  acid  (one-half 
per  cent — the  official  form  is  supposed  to  be  two  per  cent^ 
but  is  usually  much  weaker  and  often  unreliable)  and  so- 
dium sulphide  (one  per  cent). 

When  all  adjustments  are  made  take  a  normal  record 
showing  at  least  one  or  two  notches  for  the  oxygen  con- 
sumption tracing.  Then  inject  one-half  cubic  centimeter 
of  the  cyanide  solution.  Marked  results  should  be  shown 
on  all  three  tracings.  The  dose  may  be  too  small  if  3^our 
drug  was  deteriorated  (as  is  very  often  the  case — ouly  fresh 
preparations  should  be  used).  Very  small  doses  of  the 
cyanides  do  not  affect,  or  possibly,  may  even  slightly  in- 
crease the  rate  of  oxygen  consumption.  Large  doses  de- 
crease the  rate  and  your  records  should  easily  show  this 
action. 

When  the  animal  returns  to  normal  again  inject  a  dose 
(perhaps  one  cubic  centimeter)  of  cyanide  and  note  the  ef- 
fect. Get  the  oxygen  consumption  record  over  three  or 
four  notches  to  see  the  prolonged  action  of  the  drug  on  this 
function.  Let  the  animal  recover  and  give  a  third  injection 
of  cyanide.  When  the  symptoms  become  marked  inject  one 
cubic  centimeter  of  the  sodium  sulphide  solution  (sodium 
liyposulphite  may  be  substituted)  and  determine  Avliether 
or  not  this  aids  materially  in  the  recovery  of  the  animal. 
What  antidotes  do  you  know  for  cyanide  poisoning?  How 
are  these  administered!  How  quickly  could  tbis  be  done? 
Hov.'  quickly  will  the  cyanide  act  ? 


442  EXPEEIMENTAL   PHARMACOLOGY 


Fig.  347. — Tracing  showing  the  action  of  sodium  cyanide  on  the  rate  of  oxygen  con- 
sumption, blood-pressure  and  respiration  of  a  dog.  Oxygen  was  given  in  ISO  c.c.  quantities 
at  a  time. 


ACTION    OF    CYANIDES 


443 


Allow  the  animal  to  recover  and  watch  carefully  for  the 
appearance  of  an  irregular  form  of  respiration.  Cheyne- 
Stokes  respiration  is  often  produced  by  cyanides.  Inject 
some  more  sodium  sulphide  after  a  time  to  see  how  the 
drug  acts  then.  How  does  the  sulphide  affect  the  oxygen 
consumption  ? 


Fig. 


348. — Tracing   showing   the    action    of   potassium    cyanide    on    the    blood-pressure    and 
respiration  of  a  dog  anesthetized  with  nitrous  oxide. 


If  the  animal  is  still  in  fair  condition  (as  it  probably  is) 
insert  a  straight  cannula  into  one  femoral  artery  and  draw 
off  five  cubic  centimeters  of  blood  into  a  test  tube.  Then 
pour  one  cubic  centimeter  of  your  cyanide  solution  into  the 
blood,  shake  up  the  mixture  and  examine  its  color  closely. 


444 


EXPERIMENTAL   PHAEMACOLOGY 


r-     C 


ACTION    OF    CYANIDES 


445 


Set  the  tube  aside  and  see  whether  or  not  clotting  occurs. 
What  action  have  cyanides  on  the  coagulation  of  blood! 
How  is  this  brought  about? 

Draw  off  another  five  cubic  centimeters  of  blood  and 


i-i'A,iii^^ 


X 


miuMu 


Fig.  350. — Myocardiogi-arhic  and  biood-pressure  tracings  showing  tlie  action  of  2  c.c.   of  a 
dilute   sodinm   cyanide   solution. 


446  EXPERIMENTAL   PHARMACOLOGY 

then  pour  a  few  drops  of  hydrogen  peroxide  into  the  test 
tube.  What  happens  when  the  peroxide  mixes  with  the 
blood?  Is  the  color  of  the  blood  changed?  Now  draw  off 
another  five  cubic  centimeters  of  blood  and  pour  two  cubic 
centimeters  of  cyanide  solution  into  the  test  tube.  Shake 
up  the  mixture  and  then  add  hydrogen  peroxide  to  the  test 
tube.  Do  you  get  any  frothing  of  the  mixture?  Why? 
Does  the  solution  remain  bright  red?  How  do  you  explain 
this?  Save  the  test  tubes  and  examine  each  (in  one-half 
cr  one  per  cent  solution)  spectroscopically  (if  you  have  a 
spectroscope)  after  the  animal  dies.  A  tube  of  normal  blood 
to  which  a  little  (one  per  cent)  sodium  citrate  solution  has 
been  added  may  also  be  saved  for  comparing  the  spectra  of 
the  different  samples. 

Now  pass  a  catheter  into  the  bladder  (if  you  can)  and 
draAv  off  some  urine.  If  you  cannot  pass  the  catheter,  open 
the  abdomen,  isolate  the  bladder,  and  insert  a  large  hypo- 
dermic needle  through  the  bladder  wall  and  draw  off  some 
urine.  Test  this  urine  with  Fehling's  or  Haine's  solution 
for  sugar.  If  you  get  a  positive  test,  how  do  you  explain 
the  cause  of  the  glycosuria  ?  What  factors  are  involved  and 
what  is  the  mechanism  of  their  action?  Do  you  know  of 
any  other  drugs  that  have  a  similar  action?  Give  a  large 
dose  of  cyanide  and  as  soon  as  the  respiration  stops  start 
artificial  respiration  to  see  if  you  can  revive  the  animal. 
This  is  often  successful  when  the  dose  is  not  too  large.  Re- 
covery usually  occurs  fairly  rapidly  if  the  dose  is  of 
moderate  size.  Kill  the  animal  with  cyanide.  What  is  the 
size  of  the  fatal  dose  ?  How  does  this  compare  with  aconi- 
tine  or  strychnine  ?  Discuss  in  full  your  observations  on  the 
blood-pressure,  cardiac  inhibition,  nutrition,  treatment,  res- 
piration and  coagulation  of  the  blood. 

It  will  be  instructive  to  keep  the  dead  animal  for  a  few 
hours  to  see  if  the  blood  clots  in  the  vessels.  The  color  of 
the  blood  should  also  be  noted  after  a  few  hours.  Is  rigor 
mortis  hastened  or  delayed  in  its  appearance? 


ACTiox  OF  quininp:  447 

EXPERIMENT  CXLVIIT. 
Quinine.    (Frog:  General  Symptoms.) 

1.  Destroy  the  cerebrum  of  a  frog  and  inject  into  the 
anterior  lymph  sac  one  cubic  centimeter  of  quinine  hydro- 
chloride solution  (one  cubic  centimeter  equals  ten  milli- 
grams). Put  tlie  frog  in  a  quiet  place,  count  the  rate  of 
lymph  heart  beats  and  of  the  heart  beats.  Observe  the  ani- 
mal carefully  as  the  action  of  the  drug  comes  on.  Are 
there  any  signs  of  central  nervous  stimulation  f  How  is  the 
rate  of  beat  of  the  heart  and  of  the  lymph  hearts  affected! 
Do  the  reflexes  persist?  Can  you  elicit  a  pupillary  light  re- 
flex ?  Save  the  animal  to  see  if  it  survives  the  action  of  the 
drug?  What  conclusions  can  you  draw  from  the  experi- 
ment ? 

EXPERIMENT  CXLIX. 
Quinine.    (Frog  or  Turtle:  Heart  Tracing.) 

1.  Arrange  a  frog  or  turtle  for  taking  heart  tracings. 
Make  a  normal  record  showing  vagus  stimulation.  Then 
irrigate  the  heart  with  quinine  hydrochloride  solution  (one 
cubic  centimeter  equals  ten  milligrams).  What  effect  has 
the  drug  on  the  heart  muscle  and  on  the  nervous  inhibitory 
apparatus  1 

EXPERIMENT  CL. 

Quinine.     (Frog:  Action  on  White  Corpuscles — Binz's 
Experiment.) 

1.  Pith  a  frog  and  make  a  longitudinal  incision  in  one 
side  of  the  abdomen.  Carefully  pull  a  loop  of  intestine 
{leaving  the  mesentery  intact)  out  through  the  incision. 
Place  the  frog  on  a  thin  board  similar  to  that  illustrated  in 
Fig.  305,  but  which  lias  a  circular  hole  about  one  inch  in 


448  EXPERIMEISTTAL   PHARMACOLOGY 

diameter  in  the  side  nearest  the  microscope.  This  hole 
should  be  near  the  middle  of  the  length  of  the  board  and 
about  one-fourth  inch  from  the  side  of  the  board  (next  to 
the  microscope).  A  cork  is  passed  into  the  hole  (tightly) 
and  then  a  second  hole  about  one -half  inch  in  diameter  is 
bored  through  the  cork  so  that  the  mesentery  of  the  frog 
can  be  stretched  out  over  the  hole  in  the  cork  and  thus 
brought  under  the  objective  of  the  microscope.  Pin  down 
the  loop  of  the  intestine  to  the  upper  surface  of  the  cork  and 
thus  secure  a  flat  surface  of  the  mesentery  for  observations. 
The  upper  surface  of  the  cork  should  be  about  one-fourth 
inch  above  the  surface  of  the  board.  Use  the  low  power  ob- 
jective and  observe  the  blood  flow  through  the  mesenteric 
capillaries.  Examine  the  white  corpuscles  carefully.  Ob- 
serve how  they  move  along  next  to  the  capillary  walls  or 
pass  out  slowly  into  the  tissues.  Do  you  see  any  lympho- 
cytes? The  exposure  and  manipulation  of  the  tissues  of  the 
mesentery  will  produce  sufficient  inflammation  to  cause  an 
accumulation  of  leucocytes  in  the  area  involved.  After  you 
have  fully  familiarized  yourself  with  the  appearance  and 
action  of  these  leucocytes  then  inject  into  the  anterior  lymph 
sac  of  the  animal  two  cubic  centimeters  of  quinine  hydro- 
chloride solution  (one  cubic  centimeter  equals  ten  milli- 
grams) and  watch  the  actions  and  distribution  of  the  leu- 
cocytes as  the  drug  is  absorbed.  Do  the  white  corpuscles 
still  cling  to  the  lining  of  the  vessels,  or  do  they  pass  out 
into  the  neighboring  tissues'?  What  conclusions  can  you 
draw!  What  relation  does  the  action  of  the  quinine  on  the 
white  corpuscles  bear  to  the  action  of  quinine  on  the  Plas- 
modium of  malarial  fever!  What  general  conclusions  can 
you  draw  from  the  experiment! 

Quinine  is  often  injected  intravenously  in  severe  cases  of 
malarial  infection  in  man.  This  form  of  treatment  is  effec- 
tive, and  rapid  results  ma^''  be  obtained.  From  the  above 
experiment  what  action  do  you  infer  the  quinine  thus  thrown 
rapidly  into  the  blood  will  have  on  malarial  organisms  (pro- 
vided the  concentration  of  the  drug  is  great  enough) ! 


ANTIPYRINE    AND    /?-TETRAHYDROISrAPHTHYLAMINE  449 

EXPERIMENT  CLl. 
Antipyrine.    (Frog:    General  Action.) 

1.  Into  the  anterior  lymph  sac  of  a  frog  inject  two  cubic 
centimeters  of  antipyrine  solution  (one  cuhic  centimeter 
equals  ten  milligrams).  Put  the  frog  in  a  quiet  place  and 
observe  its  actions  closely.  Are  the  reflexes  stimulated  or 
depressed!  Is  there  developed  somnolence  or  convulsions? 
How  is  the  central  nervous  system  atfected? 

EXPERIMENT  CLII. 

Antipyrine,  /3-tetrahydronaphthylamine  Hydrochloride. 
(Dog:  Respiration,  Blood-pressure,  Leg  Volume.) 

1.  Arrange  a  dog  for  recording  blood-j)ressure,  respira- 
tion and  the  volume  changes  of  the  left  hind  leg  (plethys- 
mograph).  Take  the  animal's  temperature  at  ten  minute 
intervals.  Place  antipyrine  solution  (one  cubic  centimeter 
ecpials  ten  milligrams)  and  j8-tetrahydronaphtliylamine  hy- 
drochloride (one  cubic  centimeter  equals  live  milligrams) 
in  the  two  injecting  burettes  (in  the  right  femoral  and  left 
external  jugular  veins). 

Take  a  normal  record  and  then  inject  one  cubic  centi- 
meter of  antipyrine.  How  is  the  heart  affected!  The  res- 
piration? Do  you  get  a  change  in  leg  volume?  If  so  what 
does  this  signify?    Wait  for  the  animal  to  return  to  normal. 

Inject  two  cubic  centimeters  of  /^-tetrahydronaphthjda- 
mine  solution  (watch  the  pupils  and  eyelids  closely  as  this 
is  done).  Do  you  get  a  change  in  leg  volume?  (The  rub- 
ber cuff  must  fit  tightly  to  the  skin  of  the  leg  which  must 
be  shaven  closely — you  cannot  make  the  cuff  hold  air  if  the 
hair  is  left  on  the  leg.  Avoid  vaseline  for  this  purpose.) 
How  does  the  action  of  the  /?-tetrahydronaplitliylamine  com- 
pare with  that  of  antii^yrine  on  the  blood-pressure,  res- 
Xjiration,  temperature  controlling  mechanism  and  leg  vol- 


450 


EXPERIMENTAL   PHARMACOLOGY 


ume?  Is  it  possible  to  determine  the  action  of  such  drugs 
as  antipyrine  or  /S-tetrahydronaphthylamine  on  the  heat 
regulating  mechanism  in  a  brief  interval  of  time,  e.  g.,  in 
ten  minutes?    On  what  do  you  base  your  conclusions? 

From  time  to  time  inject  more  antipyrine  and  see  what 
later  actions  the  drug  has.     Further  injections  of  jS-tetra- 


Fig.  351. — Tracing  showinor  the  action  of  pilocaroine  and  j8-tetrahydronaphthylamine  hydro- 
chloride   on    the   bronchioles    and    blood-pressure    in   a    spinal    dog. 

hydronaphthjdamine  may  also  be  made  to  get  satisfactory 
tracings.  Kill  the  animal  with  antipyrine.  A¥hat  s^anptoms 
are  produced  and  what  is  the  immediate  cause  of  death  ? 

iS-tetrahydronaphthylamine  belongs  to  a  class  of  drugs 
to  which  the  name  ''sympatho-mimetic"  has  been  applied. 
Adrenaline  is  the  best  known  member  of  this  group.  These 
drugs  act  on  one  or  more  parts  of  the  involuntary  nervous 
system  (see  Fig.  318). 


ANTIPYRETICS  451 


EXPERIMENT  CLIII. 


Antipyrine,  Peptone.     (Two  Rabbits:  Temperature 
Regulation.) 

1.  Four  hours  before  the  class  meets  administer  hypo- 
dermically  to  each  of  two  rabbits  (one  for  a  control)  one- 
tenth  of  a  gram  per  kilogram  of  weight  of  Witte's  peptone 
(in  twenty  per  cent  solution).  Record  the  temperature  of 
both  rabbits  and  then  give  one  by  stomach  one-tenth  gram 
per  kilogram  of  w^eight  of  antipyrine.  Record  the  tem- 
perature of  each  animal  at  fifteen  minute  intervals,  and  de- 
termine whether  or  not  the  temperature  is  affected  by  the 
antipyrine. 

EXPERIMENT  CLIV. 

Quinine,  Peptone.     (Two  Rabbits:  Temperature 
Regulation.) 

1.  Repeat  the  above  experiment  but  substitute  quinine 
hydrochloride  (one-tenth  gram  per  kilo)  for  the  antipy- 
rine. Does  this  affect  the  temperature  in  any  Avay?  Dis- 
cuss the  manner  of  action  of  antipyrine  and  of  quinine  on 
the  heat  regulating  meclianism  and  on  the  reduction  of 
fever  temperature. 

EXPERIMENT  CLV. 

Phenacetine,  Acetanilide  or  Aspirin  (Acetylsalicylic  Acid). 
(Fevered  Animal:  Temperature.) 

1.  Watch  the  stock  of  animals  during  the  period  when 
the  antipyretics  are  being  studied  and  if  an  animal  be- 
comes ill  with  a  rise  in  temperature  then  administer  to  it 
by  stomach  one-tenth  gram  per  kilogram  of  weight  of  phe- 
nacetine, acetanilide,  or  aspirin.  Record  the  temperature 
at  fifteen  minute  intervals  and  see  if  any  change  occurs. 


452  EXPERIMENTAL   PHARMACOLOGY 

How  long  will  it  probably  be  before  the  fever  returns  if  the 
drug  lowers  the  temperature  to  normal?  Which  of  these 
three  drugs  is  most  effective  in  lowering  the  temperature? 


EXPERIMENT  CLVI. 
Acetylsalicylic  Acid  (Aspirin).    (Student:  Headache.) 

1.  Watch  for  a  student  or  other  person  who  has  a  head- 
ache due  presumably  to  "migraine."  Consult  the  instruc- 
tor and  if  the  person  affected  with  the  headache  is  other- 
wise normal  give  him  by  stomach  a  five  grain  tablet  of 
acetylsalicylic  acid.  Observe  the  action  of  the  drug  and 
see  if  the  headache  is  not  decreased  in  about  fifteen  or 
twenty  minutes.  The  drug,  in  reasonable  doses,  is  not  dan- 
gerous and  often  entirely  stops  certain  types  of  headache. 
Mter  half  an  hour  another  five  grain  tablet  may  be  taken 
if  absolutely  necessary.  Do  you  know  of  any  other  drugs 
that  might  be  used  here  instead  of  the  acetylsalicylic  acid  ? 
If  so  what  sized  doses  should  be  given? 

EXPERIMENT  CLVII. 

Phenylsalicylate  (Salol).     (Student:  Excretion, 
Absorption.) 

1.  Take  by  mouth  a  capsule  containing  five  grains  of 
salol.  This  is  decomposed,  on  reaching  the  intestine,  into 
phenol  and  salicylic  acid.  Test  the  urine  for  salicylic  acid 
by  adding  a  few  drops  of  ferric  chloride  when  a  violet  color- 
ation appears.  A  positive  test  should  be  observed  in  one 
to  one  and  one-half  hours.  This  is  Ewald's  test  for  the 
motility  of  the  stomach  but  a  dose  as  large  as  one  gram 
has  been  recommended  for  this  purpose.  The  U.S.P.  dose 
is  five  grains.  (For  literature,  see  Hanzlik,  P.  J.:  Reports 
of  Therapeutic  Research  Committee,  A.  M.  A.,  1914,  3,  131.) 


iS-TETRAHYDEONAPHTHYLAMlNE    AND    PILOCARPIJSTE         453 

EXPERIMENT  CLVIII. 

/?-tetrahydronaphthylamine     Hydrochloride,     Pilocarpine. 

(Dog:  Oxygen  Consumption,  Blood-pressure, 

Respiration.) 

1.  Arrange  a  dog  (eiglit  or  ten  kilos)  for  recording  oxy- 
gen consumption,  blood-pressure  and  respiration.  (Give  a 
small  dose  of  cliloretone.)  The  injecting  burettes  contain 
)5-tetrahYdronaplithylamine  hjTlrochloride  (one  cubic  cen- 
timeter equals  five  milligrams)  and  pilocarpine  (one  cubic 
centimeter  equals  one  milligram.) 

When  all  adjustments  are  made  take  a  normal  record 
(showing  at  least  two  notches  of  the  oxygen  record).  Then 
inject  tAvo  cubic  centimeters  of  the  /?-tetrahydronaplitliyla- 
mine  (watch  the  pupils)  and  record  the  results.  How  is 
the  rate  of  oxygen  consumption  affected?  Wait  for  the 
drug  to  act  and  see  if  all  records  return  again  to  normal. 

Then  give  one  cubic  centimeter  of  pilocarpine.  Watch 
the  rate  and  depth  of  the  respiratory  movements  as  the 
drug  begins  to  act  and  wait  a  little  while  for  this  to  develop. 
The  action  of  pilocarpine  is  rather  prolonged  and  may  in- 
crease in  intensity  for  about  one  minute,  or  in  some  organs 
for  even  a  longer  period.  Is  there  any  difficulty  in  either 
expiration  or  inspiration?  What  did  the  oxygen  record 
show  just  after  the  pilocarpine  was  injected?  How  do  you 
account  for  this?  What  kind  of  an  effect  on  the  oxygen 
record  Avould  a  drug  show  if  it  acted  in  a  manner  exactly 
the  opposite  to  that  of  pilocarpine  ? 

When  the  pilocarpine  action  becomes  well  marked  (give 
another  one  cubic  centimeter  if  absolutely  necessary)  then 
inject  a  dose  (probably  three  or  four  cubic  centimeters  of 
iS-tetrahydronaphthylamine — estimate  a  good  sized  dose  by 
your  previous  result)  and  see  how  this  drug  counteracts 
the  pilocarpine.  How  is  the  oxygen  record  affected?  How 
do  you  account  for  this?  Do  you  know  of  any  other  drug 
that  resembles  jS-tetrahydronaphthylamine  in  action? 


454  EXPERIMEN^TAL  PHARMACOLOGY 

Record  the  temperature  of  the  animal  from  time  to  time 
and  see  if  you  can  produce  a  hyperthermia  by  injecting 
/?-tetrahydronaphthylamine.  Will  the  narcosis  prevent 
this  rise  in  temperature  in  your  animal  ?  How  does  the 
drug  act  to  produce  a  fever  temperature!  Kill  the  animal 
by  injecting  /8-tetrahydronaphthylamine.  After  death  test 
the  urine  for  reducing  bodies.  What  conclusions  can  you 
draw  from  the  experiment!  Are  the  adrenal  glands  espe- 
cially involved  in  any  wa^^  in  this  exi^eriment !  If  so,  how  ? 
Are  there  any  other  drugs  that  have  this  action! 

EXPERIMENT  CLIX. 
Carbolic  Acid  (Phenol).     (Frog:  General  Action.) 

1.  Into  the  anterior  lymph  sac  of  a  frog  inject  one  cubic 
centimeter  of  a  one  per  cent  solution  of  carbolic  acid.  Put 
the  frog  in  a  quiet  place  and  observe  its  symptoms.  Do 
you  note  depression  or  are  there  convulsions!  What  struc- 
tures are  involved  in  the  action  of  the  drug! 

EXPERIMENT  CLX. 

Carbolic  Acid,  Sodium  Sulphate.    (Dog:  Local  Action, 

Respiration,  Blood-pressure,  Spleen  Volume, 

Antidote.) 

1.  Arrange  a  dog  for  recording  blood-pressure,  respira- 
tion and  the  volume  changes  of  the  spleen.  The  injecting 
burettes  contain  carbolic  acid  (one-half  per  cent)  and  so- 
dium sulphate  (three  per  cent). 

With  a  razor  shave  the  hair  off  of  a  spot  on  the  dog  an 
inch  or  more  in  diameter.  In  the  center  of  this  spot  put  a 
drop  of  phenol  liquef actum  (U.S.P.  about  90  per  cent — 
make  this  from  the  crystals  by  adding  a  very  little  water  to 
some  of  the  substance  in  a  test  tube  and  heating  gently  till 
solution  is  effected.    How  does  this  preparation  differ  from 


CARBOLIC    ACID 


455 


Fig.  352.— Two  tracings  (joined  together)  showing  the  action  of  a  drug  which 
markedly  lowers  blood-pressure,  on  the  intestinal  volume,  spleen  volume,  blood-pressure 
and  respiration.  See  if  you  can  find  a  drug  which  produces  this  kind  of  a  tracing  and 
determine  the  difference  between  active  and  passive  effects  on  oncometer  tracings. 


456  EXPERIMENTAL   PHARMACOLOGY 

a  simple  solution  of  the  crystals  in  water  f  Only  about  five 
per  cent  of  the  drug  can  be  dissolved  in  water.) 

Watch  the  action  of  the  drug  on  the  skin  closely,  noting 
color  changes,  etc.  After  a  short  time  wipe  off  the  phenol 
and  see  what  kind  of  a  scar  is  left.  Quickly  sponge  95  per 
cent  alcohol  thoroughly  over  the  spot  and  see  how  the  color 
and  appearance  of  the  area  are  affected.  Of  what  practical 
use  may  this  be  to  you  1  What  antidote  would  you  apply  if 
carbolic  acid  had  been  swallowed  1  In  Avhat  strength  would 
you  use  the  antidote  and  what  precautions  would  you  take 
to  prevent  its  absorption?  Proceed  quickly  with  the  ex- 
periment. 

When  all  adjustments  are  made  take  a  normal  record 
and  inject  five  cubic  centimeters  of  carbolic  acid  solution. 
A¥ait  for  the  drug  to  act.  When  the  records  return  to  nor- 
mal again  inject  five  cubic  centimeters  of  the  phenol  solu- 
tion. What  differences  do  you  note  between  the  effects 
produced  by  the  two  injections?  After  a  time  inject  more 
of  the  phenol  and  bring  on  a  marked  reaction  (be  sure  the 
sodium  sulphate  is  ready  and  that  the  injecting  cannula  is 
not  closed  off  by  a  clot).  When  the  animal  is  greatly  de- 
pressed note  its  condition  (muscular  twitchings,  etc.) 
closely  and  begin  to  inject  the  sulphate  solution  (in  two 
cubic  centimeter  doses  frequently  repeated).  What  effect 
has  this  on  the  animal?  How  do  you  explain  the  result? 
See  if  you  can  get  the  animal  to  return  to  normal. 

After  a  time  stimulate  one  vagus  nerve  and  see  if  the 
heart  is  inhibited.  Does  this  affect  the  respiration?  Now 
take  a  very  small  pledget  of  cotton,  soak  it  in  phenol  lique- 
factum  and  place  it  on  the  vagus  trunk  for  one  minute. 
Remove  the  cotton  and  stimulate  above  the  poisoned  area. 
Repeat  the  stimulation  below  the  area.  How  does  each 
stimulation  affect  the  heart  and  respiration?  What  con- 
clusions can  you  draw  ? 

With  a  stomach  tube  inject  fifty  cubic  centimeters  of 
five  per  cent  carbolic  acid  into  the  dog's  stomach  and  wait 


PHLORIDZIjST,    ADREiSrALINE,    POTASSIUM    IODIDE  457 

for  the  animal  to  die.  After  death  pass  a  trocar  into  tlie 
bladder  (or  catheterize)  and  draw  off  some  urine.  Test 
this  for  albmnen  (nitric  acid  test)  and  for  reducing  bodies 
(Fehling's  test).  Put  five  cubic  centimeters  of  urine  in  a 
test  tube  and  add  a  few  drops  of  ferric  chloride  solution. 
If  you  get  a  color  reaction  what  does  it  mean?  Put  some 
of  the  urine  in  a  beaker  and  set  it  aside  until  next  day  to 
observe  any  later  changes  in  color.  Open  the  stomach  care- 
fully (over  a  sink)  and  examine  closely  the  condition  of 
the  gastric  mucosa.  What  would  the  stomach  lining  show 
if  sectioned  and  examined  histologically?  Do  this  if  you 
can.  What  conclusions  can  you  draw?  How  is  carbolic 
acid  excreted  ?  What  is  the  fate  of  the  drug  in  the  tissues  ? 
(See  Sollmann,  Brown,  Clarke:  Journal  American  Medical 
Association,  1906,  March  17,  and  1907,  March  23 ;  also  Jour- 
nal of  Pharmacology,  i,  p.  409.) 

EXPEEIMENT  CLXI. 
Phloridzin,  Adrenaline.     (Rabbit:  Glycosuria.) 

1.  Dissolve  one-fourth  gram  of  phloridzin  in  warm  water, 
and  inject  it  subcutaneously  into  a  rabbit.  Obtain  a  sam- 
ple of  the  urine  at  the  end  of  two  hours,  by  pressure  on 
the  abdomen  with  the  thumb  or  by  passing  a  catheter,  and 
test  for  sugar.  If  none  is  present  wait  some  time  longer 
and  again  test  the  urine  (Stewart).  Glycosuria  may  also 
be  produced  by  injecting  subcutaneously  into  a  rabbit  one 
or  two  cubic  centimeters  of  adrenaline  (1:1000).  The  rab- 
bits should  be  placed  in  a  cage  where  the  urine  can  be  col- 
lected. 

EXPEEIMENT  CLXII. 

Potassium  Iodide.     (Student:  Absorption,  Excretion.) 

1.  Take  by  mouth  a  capsule  containing  five  grains  of 
potassium  iodide.  (Iodides  have  to  be  used  with  care  in 
cases  of  pulmonary  phthisis.) 


458  EXPERIMEI^TAL   PHARMACOLOGY 

At  one  minute  intervals  after  the  drug  is  swallowed  test 
the  saliva  (on  a  white  pill  tile  or  glass  plate  on  a  sheet  of 
paper)  by  adding  saliva  to  three  per  cent  starch  paste 
(slightly  acidified  by  HNO3).  A  positive  test  should  ap- 
pear within  ten  to  fifteen  minutes  if  absorption  be  normal. 

Test  the  urine  by  adding  a  few  drops  of  chlorine  water 
and  starch  solution.    What  conclusions  can  you  draw  ? 

EXPERIMENT  CLXIII. 

Alkalies,  Acids,  Sodium  Nitrite,  Adrenaline.     (Frog:   Per- 
fusion of  Vessels.) 

1.  Pith  a  frog,  expose  its  heart  and  tie  a  fine  cannula  into 
one  aorta  (pointing  away  from  the  heart)  including  the 
other  aorta  in  the  ligature.  Hang  the  frog  up  by  the  lower 
jaw  and  place  a  graduated  cylinder  beneath  the  animal. 
By  means  of  a  Y-tube  connect  two  funnels  (or  small  bottles 
with  outlets  at  the  bottom)  to  the  cannula  in  the  aorta. 
Suspend  the  funnels  or  bottles  at  a  height  of  six  or  seven 
inches  above  the  heart.  One  funnel  (or  bottle)  is  filled  with 
NaOH  solution  (one-tenth  per  cent  in  Ringer's  or  tapwater 
saline  solution)  and  the  other  with  HCl  solution  (one-tenth 
per  cent  in  Ringer's  or  tapwater  saline  solution).  Snip  the 
sinus  venosus  so  that  the  fluid  can  pass  through  the  entire 
system  of  blood  vessels  from  the  beginning  of  the  aorta.  Be 
sure  all  the  air  is  out  of  the  tulles  and  that  the  flow  of  each 
solution  can  be  stopped  or  started  b}^  means  of  clips  on  the 
connecting  tubes.  Fill  the  tubes  with  the  acid  solution  and 
start  the  perfusion.  Catch  the  outflow  below  the  frog  in 
the  graduated  cylinder  and  determine  its  amount  for  three 
or  five  minute  intervals. 

Then  change  to  the  alkali  solution  and  measure  the  out- 
flow for  a  corresponding  length  of  time.  Which  substance 
dilates  the  arterioles? 

Empty  out  the  acid  solution  and  substitute  therefor 
Ringer's  solution  containing  one-half  per  cent  sodium  ni- 


PERFUSION    OF    FROG 's    VESSELS 


459 


trite.  Perfuse  tliis  tliroiigli  tlie  vessels  of  tlie  animal  and 
see  how  the  outflow  is  affected.  Empty  the  alkali  solution 
and  place  Ringer's  solution  in  the  funnel  (or  bottle)  and 
add    one-half    cubic    centimeter    of    adrenaline    solution 


Fig.  353. — Arrangement  of  apparatus  for  perfusion  of  the  vessels  of  a  brainless  frog. 


460  EXPERIMENTAL   PHARMACOLOGY 

(1:1000)  to  the  Einger's  solution.  Perfuse  this  solution 
through  the  animal  and  compare  the  outflow  with  that  from 
the  other  solutions.  What  conclusions  can  you  draw  f  How 
do  acids  and  alkalies  compare  with  adrenaline  and  nitrites 
as  regards  their  effects  on  the  arterioles? 

EXPERIMENT  CLXIV. 

Magnesium,  Calcium.    (Rabbit:  Anesthesia,  Antagonism. — 
Meltzer  and  Auer.) 

1.  Into  a  rabbit  inject  subcutaneously  1.7  grams  of  mag- 
nesium sulphate  (in  twenty-five  per  cent  solution)  per  kilo- 
gram of  weight.  Watch  the  animal  closely  and  observe 
that  in  thirty  or  fort}^  minutes  deep  anesthesia  is  produced. 

A  ten  cubic  centimeter  hypodermic  syringe  with  a  very 
fine  point  is  now  filled  with  three  per  cent  calcium  chloride 
solution.  Place  a  bull-dog  on  the  lateral  margin  of  the 
rabbit's  ear  near  the  head  and  block  the  flow  of  blood  in 
the  marginal  ear  vein  which  will  become  engorged  with 
blood.  Insert  the  syringe  point  into  the  vein  (pointing  to- 
ward the  heart),  remove  the  bull-dog  and  inject  about  eight 
cubic  centimeters  of  the  calcium  chloride  solution.  Handle 
the  animal  carefully  and  observe  what  effect  the  calcium 
has.  What  conclusions  can  you  draw?  What  explanation 
can  you  offer?  Could  you  use  magnesium  chloride  instead 
of  the  sulphate?  Would  it  simplify  the  conditions  if  cor- 
responding salts  (chloride)  of  the  metals  were  used? 

EXPERIMENT  CLXV. 

Arsenic.     (Dog  or  Rabbit:    Respiration,   Blood-pressure, 
Peristalsis,  Renal  Action,  Blood.) 

1.  Prepare  a  dog  (or  rabbit — two  grams  of  ure thane) 
for  recording  blood-pressure,  respiration  and  intestinal  con- 
tractions.   Insert  a  bladder  cannula  (avoid  hemorrhage  into 


ACTION    OF    ARSEN-IC  461 

tlie  bladder)  or  pass  a  catheter  and  draw  off  all  the  urine 
in  the  bladder.  Test  this  for  glucose,  albumen  and  casts 
(centrifuge  and  use  the  precipitate  for  microscopic  observa- 
tions). The  injecting  burette  contains  sodium  arsenate  so- 
lution (one  per  cent). 

Draw  off  one  cubic  centimeter  of  blood  from  the  femoral 
artery  and  add  to  it  one-half  cubic  centimeter  of  one  per 
cent  copper  sulphate  solution.  Draw  off  another  cubic  cen- 
timeter of  blood  and  add  to  it  one-half  cubic  centimeter  of 
sodium  arsenate  solution  (one  per  cent).  Shake  up  both 
tubes  and  observe  them  carefully.  What  conclusions  can 
you  draw?    Of  what  immediate  importance  is  this  to  you? 

When  all  adjustments  are  made  take  a  normal,  record 
the  time  of  day  and  inject  one  cubic  centimeter  of  arsenic 
solution.  How  are  the  blood-pressure  and  respiration  af- 
fected! Wait  a  while  and  then  inject  another  cubic  centi- 
meter. How  does  the  reaction  to  this  dose  correspond  with 
that  produced  by  the  first  dose  ? 

Continue  the  injections  (small)  slowly  and  allow  the 
drug  to  be  fully  distributed  to  all  the  tissues.  The  drug 
should  act  for  a  long  time  (several  hours)  to  produce  the 
most  marked  lesions.  Keep  the  animal  alive  as  long  as  you 
can  and  from  time  to  time  inject  as  much  of  the  arsenic  as 
the  animal  will  tolerate.  Obtain  specimens  of  urine  occa- 
sionally and  test  for  albumen  and  for  reduction  of  Fehling's 
solution.  Do  you  detect  any  indications  of  an  action  on 
the  alimentary  tract  ?  How  does  the  drug  act  here !  What 
renal  structures  are  especially  affected  by  the  substance? 

Near  the  end  of  the  exercise  kill  the  animal  with  the 
drug.  Test  the  urine  for  albumen,  glucose,  and  casts.  Are 
there  any  blood  cells  in  the  urine  (centrifuge  and  put  a 
drop  of  the  sediment  on  a  slide,  cover  with  a  cover  slip 
and  examine  microscopically)  ?  Open  the  abdomen,  pick 
up  the  small  intestine  and  incise  it  longitudinally.  What 
is  the  nature  of  the  contents?  Examine  tlie  mucosa  care- 
fully for  congestion  and  hemorrhages.    Save  a  piece  of  the 


462  EXPERIMENTAL   PHARMACOLOGY 

intestine  and  examine  it  histologically  for  changes  in  the 
mucosa,  etc.  Is  the  stomach  similarly  affected?  How  did 
the  drug  reach  these  organs!  Excise  one  kidney,  preserve 
and  section  it  for  microscopic  examination.  Examine  the 
liver,  lungs,  spleen,  mesentery,  etc.,  and  see  if  3^ou  can  de- 
tect any  abnormal  changes  in  them.  What  general  con- 
clusions can  you  draw  from  the  experiment? 


EXPEETMENT  CLXVI. 

Antimony  (Tartar  Emetic).     (Dog:  Emesis.) 

1.  Stir  up  forty  to  fifty  milligrams  of  tartar  emetic  ( Anti- 
monii  et  Potassii  Tartras)  in  thirty  cuIdIc  centimeters  of 
water  and  administer  through  a  stomach  tube  to  a  dog. 
Put  the  animal  in  a  quiet  place  and  observe  its  symptoms 
for  half  an  hour.  What  conclusions  can  you  draw?  Ex- 
plain in  detail  the  action  of  the  drug.  Do  you  know  of  any 
other  substance  having  a  similai'  action? 

EXPERIMENT  CLXVII. 

Vanadium,  Sodium  Hydroxide,  Ammonia.      (Dog:  Blood- 
pressure,  Respiration,  Spleen  Volume,  Reflex  and  Local 
Actions,  Intestinal  or  Bladder  Contractions.) 

1.  Arrange  a  dog  for  recording  blood-pressure,  respira- 
tion, spleen  (or  kidney)  volume  and  intestinal  or  bladder 
contractions.  Do  not  insert  a  tracheal  cannnla  at  first  hut 
carry  on  the  anesthesia  by  dropping  ether  on  a  toivel 
wrapped  around  the  dog's  nose  and  mouth.  The  injecting 
burettes  contain  ammonium  chloride  solution  (two  per  cent) 
and  sodium  ortlio vanadate  solution  (one  per  cent, — dissolve 
the  vanadium  in  water  and  neutralize  with  a  small  amount 
of  hydrochloric  acid.  .A  deep  golden  yellow  solution  is  pro- 
duced). 


ACTION    OF    VANADIUM 


Fig.  354. — Tracing  showing  the  action  of  adrenaline  sodium  orthovanadate,  amyl 
nitrite  and  adrenaline  on  the  kidney  volume,  leg  volume  (hind  limb),  blood-pressure  and 
respiration  of  a  dog.  The  first  injection  of  vanadium  usually  produces  a  more  marked 
reaction  than  those   following. 


464 


EXPERIMEE^TAL   PHARMACOLOGY 


When  all  adjustments  are  made  take  a  normal  record 
and  then  pour  a  few  drops  of  ammonium  hydroxide  solu- 
tion on  the  towel  so  that  the  animal  inhales  the  vapors. 
How  does  this  affect  the  respiration,  bladder,  spleen  vol- 
ume and  heart  rate?  How  do  you  explain  the  results? 
What  nerves  are  involved  in  the  reactions? 

Remove   the   ammonia   and   insert   a   tracheal   cannula. 


/OjSju:<r>^JA, 


Lever  onia-tnloour  bowl. 


Fig.   355. — Tracing  showing  the  action  of  vanadium  on  the  volume  of  an  excised,  perfused 
segment  of  the  small  intestine  of  a  dog. 

Take  a  normal  record  and  then  inject  one  cubic  centimeter 
of  the  ammonium  chloride  solution.  Is  this  action  identical 
in  its  origin  with  that  produced  by  the  inhalation  of  am- 
monia fumes?  Inject  a  larger  dose  of  ammonium  chloride 
to  get  satisfactory  records  if  the  first  ones  were  not  good 
enough  (but  save  the  vitality  of  the  animal  as  much  as  pos- 
sible). Empty  out  the  ammonium  chloride  solution  and 
place  adrenaline  (1:10,000)  in  the  burette. 

Allow  the  animal  to  recover  as  fully  as  possible.     Take 


ACTION    OF    VANADIUM 


465 


a  normal  record  (see  that  all  writing  pointers  are  properly 
adjusted)  and  inject  two  cubic  centimeters  of  vanadium 
solution.  Wait  for  the  action  of  the  drug  to  wear  off  and 
then  inject  one-half  cubic  centimeter  of  adrenaline.  How 
do  the  two  sets  of  records  compare?  Do  you  know  of  any 
other  metal  having  an  action  similar  to  vanadium  ?  If  nec- 
essary (to  get  good  records)  inject  another  (perhaps  larger) 
dose  of  vanadium.  On  what  structures  does  vanadium  act  ? 
Can  you  determine  this  point  from  your  experiment? 
(Could  you  separate  the  possibility  of  actions  occurring  on 


perfusion  wH^  ??in^er-»- Blood. 

^og  =  /0.!i/<iJ0S. 

Sodium  Oirthovan<i<izte.-J% 


/  (Oxf^^OTVctit^  . 


Fig.  356. — Tracing  showing  the  action  of  vanadium  on  the  volume  of  the  excised,  perfused 

spleen   of  a  dog. 

both  nerve  endings  and  smooth  muscle  fibers  by  taking  a 
record  of  the  bronchial  contractions — in  another  animal — 
produced  by  vanadium  after  atropine  has  been  given?) 
Have  you  seen  any  indications  of  an  action  on  the  intestine  ? 
How  do  you  account  for  this  1  Does  the  metal  have  a  se- 
lective action  for  the  intestine !  Do  you  know  of  any  other 
metal  that  has  a  similar  action? 

After  enough  vanadium  records  have  been  obtained  then 
inject  into  the  stomach  with  a  stomach  tube  one  hundred 
cubic  centimeters  of  ten  per  cent  (or  twenty  per  cent)  so- 
dium hydrate  solution.  Wait  for  the  animal  to  die.  (Be 
sure  the  anesthesia  is  deep  and  regular  before  the  NaOH 


466  EXPERIMEISTTAL   PHARMACOLOGY 

is  injected.)  Clip  the  hair  and  shave  a  sn^all  area  on  the 
animal's  side.  Wet  a  pledget  of  cotton  with  twenty  per 
cent  sodium  (or  potassimn)  hydrate  solution  and  lay  the 
cotton  on  the  prepared  area.  Let  it  stay  for  some  time 
and  then  examine  the  condition  of  the  skin  on  the  area. 
AVhat  conclusions  can  you  draw!  Wet  another  pledget  of 
cotton  with  dilute  acetic  acid  and  place  this  on  the  area. 
See  if  this  in  any  way  changes  the  character  of  the  results 
produced  by  the  alkali.  What  conclusions  can  you  draw? 
After  death  remove  the  stomach  and  the  upper  end  of 
the  small  intestine  (cut  between  double  ligatures)  and  open 
the  stomach  (over  a  sink).  What  changes  do  you  find  in 
the  stomach  walls?  Would  you  recognize  such  a  stomach 
at  autopsy  in  a  case  of  poisoning  I  Did  the  alkali  pass  into 
the  small  intestine?  If  so  how  far  down  did  it  go?  Did 
the  vanadium  have  anything  to  do  with  the  lesions  you 
have  observed?  Examine  (open)  the  remainder  of  the 
small  intestine  and  the  large  intestine  for  congestion  of  the 
mucosa,  petechial  hemorrhages,  etc.  If  these  are  present 
how  were  they  produced?  AVhat  general  conclusions  can 
you  draw  regarding  the  action  of  vanadium  and  of  the 
strong  alkalies? 

EXPEEIMENT  CLXVIII. 

Acid,  Alkali — Rhubarb,  Croton  Oil,  Magnesium  Sulphate. 

(Dog:  Antagonism  of  Acids  and  Alkalies,  Absorption 

and  Excretion  of  Rhubarb,  Local  Action  of  Croton 

Oil  and  Magnesium  Sulphate — Moreau's 

Experiment.) 

1.  Etherize  a  dog  and  arrange  to  record  blood-pressure 
and  respiration.  Insert  a  bladder  cannula  (or  catheter) 
and  collect  the  urine.  Test  some  urine  at  once  by  adding 
a  little  ten  per  cent  sodium  hydrate  to  a  few  cubic  centi- 
meters of  urine.    If  no  color  change  occurs  add  a  drop  or 


PRELIMINARY    OPERATIONS 


467 


two  of  plienolphtlialein  solution.  The  injecting  burettes 
contain  one-half  per  cent  lactic  acid  and  one  per  cent  sodium 
carbonate  solution. 

Open  the  abdomen  and  with  the  greatest  care  not  to 
manipulate  the  intestines  more  than  can  be  helped,  pick 
up  the  duodenum  and  with  a  hypodermic  syringe  inject 
into  the  lumen  of  the  gut  five  cubic  centimeters  of  fluid- 
extractum  rhei,  U.S.P.  Replace  this  part  of  the  intestine 
and  then  going  as  far  as  possible  down  the  small  intestine 
pick  up  the  ileum  and  tie  four  ligatures  around  the  gut  as 
sliowm  in  Fig.  357,  thus  isolating  three  loops  of  the  intestine 
each  about  three  inches  long.    Into  the  first  of  these  loops 


Fig.   357. — Arrangement  of  the  ligatures  for  isolating  segments  of  the  intestine  in 
Moreau's  experiment. 

(which  should  be  tied  with  a  colored  ligature)  inject  five 
cubic  centimeters  of  normal  salt  solution.  Into  the  middle 
loop  inject  five  cubic  centimeters  of  normal  salt  solution  to 
which  half  a  drop  of  croton  oil  has  been  added.  Into  the 
third  loop  inject  five  cubic  centimeters  of  twenty-five  per 
cent  magnesium  sulphate  solution.  Carefully  replace  the 
intestine,  close  the  abdomen  and  prepare  to  take  some  rec- 
ords on  the  drum.  If  the  animal  is  doing  well  it  is  prefer- 
able to  wait  half  an  hour  or  so  to  allow  the  drugs  in  the 
intestine  to  act.  As  soon  as  some  urine  is  secreted  observe 
its  color  closely.  Then  add  a  little  sodium  hydrate  and  note 
any  changes.    What  are  the  active  principles  of  rhubarl)  ? 


468  EXPERIMEI^TAL   PHAKMACOLOGY 

What  is  emodin?  How  is  rhubarb  excreted!  How  is  the 
urine  influenced  by  the  drug?  What  does  the  addition  of 
alkali  to  the  urine  show?  Do  you  know  of  au}^  other  drugs 
that  produce  similar  results? 

Take  a  normal  tracing  and  inject  one-half  cubic  centi- 
meter of  lactic  acid  solution.  Wait  a  little  while  for  the 
acid  to  act.  Are  there  any  symptoms  of  embolism?  In- 
ject more  acid  from  time  to  time  and  note  the  action  on 
respiration,  blood-pressure  and  the  heart.  Do  you  know 
of  any  pathological  condition  in  which  similar  s^miptoms 
may  occur?  Inject  acid  until  very  marked  symptoms  are 
produced.  Be  able  to  describe  these  symptoms  accurately. 
Now  inject  some  of  the  sodium  carbonate  solution  and  see 
how  this  affects  the  animal.  Continue  the  injections  of 
carbonate  for  a  while  and  see  if  you  can  get  the  animal  to 
return  to  normal.  In  what  pathological  conditions  might 
the  injection  of  sodium  carbonate  solution  be  of  benefit? 

Get  the  animal  intp  as  good  condition  as  possible  and 
then  inject  into  the  stomach  fifty  cubic  centimeters  of  ten 
per  cent  nitric  acid.  (Be  sure  the  anesthesia  is  satisfac- 
tory.) 

Examine  the  color  of  the  urine  secreted.  Add  a  few 
drops  of  ten  per  cent  NaOH  solution  and  explain  any 
change  that  may  occur. 

Open  the  abdomen  and  examine  the  intestinal  loops. 
What  is  the  condition  of  each?  The  normal  salt  solution 
should  produce  no  change.  The  croton  oil  produces  an  in- 
flammatory exudate.  This  is  a  different  action  from  that 
produced  by  ordinary  therapeutic  doses  of  the  purgatives, 
such  as  castor  oil.  How  do  these  bodies  act  in  therapeutic 
doses?  The  magnesium  sulphate  should  attract  more  fluid 
into  the  intestinal  loop  by  osmosis.  Do  you  find  this  to  be 
the  case  ?  What  can  you  say  about  the  ease  of  absorption 
of  the  saline  purgatives?  How  do  these  bodies  act  thera- 
peutically? Does  yo.ur  experiment  demonstrate  this  point? 
What  is  the  Bayliss-Starling  intestinal  reflex? 


ACTION    OF    NITRIC    ACID  469 

After  the  animal  is  dead  excise  the  stomach  and  examine 
the  walls  and  mucosa  carefully.  Do  you  find  any  changes! 
Could  you  recognize  these  at  the  autopsy  in  a  case  of  poi- 
soning? How  do  the  lesions  compare  with  those  produced 
in  the  stomach  by  NaOH  solution!  Are  there  any  char- 
acteristic color  changes  in  the  involved  tissues?  If  a  pa- 
tient thus  poisoned  by  swallowing  a  corrosive  poison  should 
recover  with  what  later  complications  might  he  be  affected  ? 
Would  this  hold  for  carbolic  acid  also?  What  do  you 
know  about  cicatrix  (scar)  formation  after  corrosive  poi- 
soning?   From  wdiat  cause  may  persons  thus  affected  die? 

Pour  a  few  drops  of  sulphuric  acid  on  a  small  area  of  the 
stomach  mucosa.  Watch  the  changes  in  the  appearance  of 
the  tissues.    Repeat  with  hydrochloric  acid. 


PART  11. 

CHAPTER  I. 
SHOP  WORK. 

The  Shop. — One  of  the  most  vahiable  assets  which  a 
modern  pharmacological  laboratory  can  possess  is  a  well- 
equipped  shop  controlled  by  a  skilled  mechanician.  While 
the  expense  of  these  may  be  too  great  for  many  laboratories 
their  value  should  be  duly  emphasized,  in  order  that  those 
who  may,  from  time  to  time,  find  themselves  in  position 
to  equip  a  shop,  or  to  hire  a  mechanic,  may  not  hesitate  to  do 
so.  It  is  always  advisable  to  buy  a  first  class  equi]3ment  if 
the  available  funds  are  sufficient.  But  if  only  a  small 
amount  of  money  is  obtainable  the  judicious  expenditure  of 
the  sum  for  the  right  tools  and  supplies  may  yield  exceed- 
ingly satisfactory  returns.  And  if  a  special  mechanic  can- 
not be  obtained  the  technician  or  diener,  or  the  members  ot 
the  teaching  staff  themselves,  may  often  secure  most  satis- 
factory results  from  a  few  hours'  work  in  the  shop.  It  is 
the  purpose  of  this  chapter  to  indicate  briefly  the  nature  of 
the  equipment  which,  in  the  author 's  opinion,  a  shop  should 
contain,  and  further,  to  give  a  few  directions  for  carrying 
out  some  of  the  more  elementarj^  and  essential  mechanical 
processes  which  will  be  of  greatest  service  in  the  laboratory. 

When  plenty  of  space  is  available  the  shop  should  be  in 
an  independent  room  which  should  be,  if  possible,  at  least 
twenty  feet  square.  A  room  twenty  by  twent3^-five  (or 
even  thirty)  feet  in  its  dimensions  is  preferable  if  it  can 
be  obtained.  This  point  should  be  carefully  considered  in 
the  building  of  ne\V  laboratories.  If  possible  the  shop 
should  receive  an  abundant  supply  of  light  from  the  north. 


ELECTRIC    WIRINCI    SYSTEM 


471 


and  a  good  supply  of  artificial  light  should  bo  provided, 
especially  in  the  form  of  drop  lights,  etc.,  placed  near  the 
work  benches,  the  lathe,  or  other  special  machines.  If 
only  a  small  room  can  be  provided  for  the  shop  (as  is 
often  the  case)  then  the  arrangement  of  the  machinery. 


\Relay 


Fig.  358. — A  schematic  representation  of  an  electric  wiring  system  for  using  an  ordi- 
nary 110  volt,  direct  current  for  regular  laboratory  purposes,  i.  e.,  for  induction  coils, 
signal  magnets,  etc.  Beginning  at  C,  and  ending  at  Y,  is  a  resistance  frame  made  of  a 
large  number  of  strips  of  thin  tinned  iron  (3.-^  inch  x  28  inches).  These  strips  are  joined 
together  at  alternate  ends  so  the  current  passes  in  series  through  the  total  length  of  all 
of  the  strips.  Small  coils  of  special  resistance  wire  may  be  used  for  this  purpose  and  is 
more  compact.  If  "tin"  strips  are  used  these  should  be  arranged  on  frames,  each  frame 
holding  about  50  or  60  strips  (the  strips  are  28  inches  long)  and  about  7  such  frames 
should  be  placed  side  by  side  in  an  insulated  cabinet.  All  frames  are  connected  together 
in  series  and  the  current  leaving  at  Y  in  the  illustration  passes  through  the  switch  and 
thence  forms  a  loop  below  the  pilot  light  which  is  connected  in  parallel  (shunt)  to  the 
main  current  wires.  The  current  leaves  the  frame  at  Z.  Small  currents  for  inductoria, 
etc.,  are  picked  off  from  the  main  frame  at  various  points  shown  at  fg,  hi,  mn,  etc.  The 
drop  (lamp  cord;  wires  (/,  /)  pass  to  the  tables  for  the  inductoria,  signal  magnets,  etc.. 
The  strength  of  current  going  to  each  table  can  be  controlled  at  will  by  varying  (by' 
means  of  a  sliding  contact;  the  distance  between  fg,  or  hi,  etc.  At  mn.  a  current  is 
taken  off  for  the  clock  circuit.  In  series  with  one  of  these  wires  is  placed  the  master 
time  clock.  It  is  advisable  to  place  a  (storage)  battery  and  small  (telegraphic)  relay  in 
this  circuit  to  protect  the  delicate  contacts  of  the  clock  which  may  be  burned  out  by  too 
strong  a  current.  From  the  main  time  circuit  wires,  O  P,  the  signal  magnets,  manometer 
base  line  signals,  etc.,  receive  the  time  signal  currents.  Signal  magnets,  etc.,  must  be 
insulated  from  the  rest  of  the  ajiparatus  if  the  main  feed  wires  to  the  building  are 
p'rounHed  pt  a""  nlace.  The  wood  board  of  the  mammeter  suffices  for  this  instrument 
liere,  but  metal  signal  magnets  may  be  insulated  by  small  pieces  of  wood  fiber  tubing  (S  in 
the  figure)  which  are  held  by  the  double  clamps.  Also  metal  writing  points  of  signal 
magnets  should  not  be  brought  against  drums  initil  the  paper  has  been  pasted  on  the  drum. 
(For  further  details,  see  Tour.  Amer.  Med.  Assoc,  1912.  58,  1011;  also  see  \'on  Hess. 
Science,  1914,  40,  566;  als'o  Yandell,  Henderson,  ibid.,  1915,  41,  910,  and  McPeek,  Reed 
and  Beck,  Journal  of  Laboratory  and  Clinical  Medicine,  1916, 'ii,  139.)  Alternating  cur- 
rent is  not  suitable  for  this  work  unless  it  can  be  changed  to  a  direct  current  by  a  special 
transformer    (see   catalogues  of   electrical   supply    houses). 


472 


EXPERIMENTAL   PHARMACOLOGY 


tools,  lighting,  etc.,  must  be  Avorked  out  independently  in 
each  laboratory.  An  arclight  which  can  be  raised  or  low- 
ered by  means  of  a  rope  passing  over  a  pulley  is  probably 
the  best  source  for  artificial  light.  In  institutions  where 
only  a  very  limited  floor  space  is  available  the  shop  work 
may  be  carried  out  in  one  end,  or  even  in  one  corner,  of 
the  class  laboratory  itself.  This  arrangement  is  by  no 
means  ideal  but  it  may  be  effective.  And  much  valuable 
work  has  been  done  under  just  such  circumstances  as  these. 
The  work  bench  or  heavy  table  should  be  placed  near  a 


Fig.   359. — Foot  bellows. 

window  if  possible.     A  second  table  for  w^ork  on  small 
articles  should  also  be  provided. 

When  possible  the  shop  should  be  located  in  a  portion 
of  the  building  from  which  noises  arising  from  the  me- 
chanical work  cannot  be  heard  in  the  libraries,  in  other 
departments^  or  in  the  lecture  room  of  the  pharmacological 
department.  In  buildings  constructed  of  concrete  or  other 
similar  material,  vibrations  from  the  shop  caused  by  the 
operation  of  a  heavy  lathe,  etc.,  may  sometimes  disturb  deli- 
cate apparatus  in  rooms  located  even  at  very  considerable 
distances  from  the  shop,  or  in  some  instances,  perhaps  in 


ARTIFICIAL   EESPIRATION    MACHINE 


473 


Fig.  360. — Diagrammatic  representation  of  an  artificial  respiration  machine.  The 
1,4  horse  power  motor  turns  a  rotary  air  pump.  Crowell's  rotary  air  pumps  (for  both 
pressure  and  vacuum)  are  advised  but  other  forms  of  pumps  are  on  the  market.  The 
second  size  (2-A)  is  sufficient  for  10  or  20  dogs  at  one  time  but  a  1/2  horse  power  motor 
should  be  used  as  the  interrupting  air  valve  should  also  be  operated  by  power  from  the 
motor.  By  opening  valves  A,  B ,  with  valves  C,  O,  closed,  a  vacuum  will  be  produced 
in  the  tank  when  the  pump  runs.  By  reversing  all  these  valves  positive  pressure  will  be 
produced  in  the  tank.  These  valves  should  be  lever  gate  valves  (Fig.  362)  which  can 
be  opened  or  closed  instantly.  Thus  changes  from  positive  to  negative  pressure  (or  the 
reverse)  can  be  made  in  about  one  second  without  stopping  the  pump.  In  some  cases  it 
is  possible  to  accomplish  this  by  reversing  the  motor.  From  the  tank  air  is  piped  (three- 
fourths  or  one-half  inch  gas  jiiping)  to  all  (larts  of  the  laboratory.  Two  main  lines  of 
piping  around  the  room  are  shown  in  the  figure.  The  feed  pipe  from  the  tank  divides 
into  two  parts  and  each  of  these  two  divisions  supplies  both  of  the  main  lines  of  piping 
around  the  room.  The  purpose  of  this  is  to  give  an  opportunity  for  one  set  of  pipes  to 
carry  a  constant  supply  of  air  (either  positive  or  negative)  while  the  other  line  may  be 
carrying  an  interrupted  current  (either  positive  or  negative).  If  two  tanks  are  used  both 
positive  and  negative  pressure  may  be  had  simultaneously,  but  with  only  one  tank  as 
illustrated  here  only  one  pressure  (either  positive  or  negative)  can.  be  had  at  one  time. 
The  pipe  carries  an  interrupting  valve  (£),  (lever  gate  valve.  Fig.  362)  which  is  inter- 
rupted at  regular  intervals  (from  25  to  40  times  or  more  per  minute).  The  large  (S  or 
10  inch)  wheel  R,  turns  the  spindle  holding  the  cone  pulleys,  1,  2,  3,  which  in  turn 
carry  the  belt  (one-inch  flat  leather  tied  together  with  belting  wire)  which  turns  the 
wheel  P.  The  wheel  P,  is  8  or  10  inches  in  diameter  and  has  a  four-inch  face.  Thus 
the  flat  (one-inch)  belt  can  be  placed  on  either  small  pulley  and  still  lie  slipped  along  the 
surface  of  the  wheel  P.  On  the  outer  edge  of  P,  is  a  hill-shaped  lug  which  raises  and 
lowers  the  pulley  L,  at  each  revolution  of  P.  It  is  important  for  L  (which  works  the 
lever  M.  and  the  bar  A'^,  which  operate  the  lever  gate  valve  E)  to  be  raised  and  lowered 
quickly  but  noiselessly,  hence  the  hill-shaped  elevation  up  and  down  the  sides  of  which  the 


474 


EXPERIMENTAL   PHARMACOLOGY 


pulley  L  rolls.  The  -zalve  E  must  be  opened  and  closed  quickly.  This  lets  a  gush  of 
air  enter  (or  leave)  the  main  lines  of  piping.  If  these  lines  were  very  short  this  sudden 
gush  of  air  might  burst  an  animal's  lungs.  It  is  to  be  emphasized,  however,  that  the 
pipe  lines  are  long  (100  feet  or  more  of  piping  may  be  used)  and  that  the  air  suddenly 
compressed  in  these  pipes  vv  11  escape  only  gradually  at  the  small  faucets  at  the  tables. 
Thus  the  period  of  inflation  of  the  lungs  may  be  as  long  as  the  period  of  deflation.  The 
danger  is  that  air  may.  continue  to  escape'  over  nearly  all  the  period  between  each  two 
successive  openings  of  the  valve.  A  slowly  opening  and  closing  valve  is  nearly  sure  to 
cause  this  difficulty. 

At  F  is  shown  a  pressure  regulating  valve.  The  e.vhaust  pipe  leading  from  this 
should  pass  up  inside  a  hood-draft  opening  in  the  wall  or  out  through  a  window  casing, 
etc.,  to  the  outside  of  the  building.  The  valve  F  is  a  screw  valve  and  when  it  is  set 
for  a  certain  opening  then  the  excess  air  compressed  in  the  tank  will  constantly  escape 
at  practically  the  same  rate  through  the  valve  F.  Thus  the  pressure  in  the  tank  is  regu- 
lated. The  pressure  gauge  is  used  for  this  regulation.  For  (positive)  artificial  respira- 
tion usually  from  3  to  5  pounds  pressure  is  needed.  Blast  lamps,  etc.,  can  be  operated 
by  this  same  air  system.  A  special  (pop-off)  pressure  regulating  valve  for  the  tank  is  on 
the  market,  but  this  valve  makes  a  most  hideous  and  disgusting  noise  in  the  laboratory. 
It  is  better  to  sirnply  let  the  excess  air  escape  to  the  outside  of  the  building  through  the 
valve  F. 

The  tank  need  not  be  large.     A  ten  or  twenty  gallon  hot  water  tank  is  sufficient. 

The  rotary  pump  costs  about  $26.00.  (A  smaller  size,  1-A,  listed  at  $^0.00  may  be 
used  for  smaller  laboratories.)  A  Yz  horse  power  motor  costs  from  about  $30.00  to  ap- 
proximately $60.00.  The  tank  may  cost  from  $4.00  tO'  $8.00.  If  a  laboratory  possesses 
fair  shop  facilities  of  its  own  such  an  air  system  can  be  installed  for  about  $75.00  to  $100.00. 
The  most  difficult  part  is  the  construction  of  the  apparatus  to  operate  the  interrupting 
valve.  This  should  be  firmly  and  reliably  constructed.  For  ten  years  the  writer  has  used 
an  artificial  respiration  machine  similar  to  that  described  above.  The  outfit  can  be 
thoroughly  recommended. 


Fig.  361. — \'iew  of  system  of  pulleys  used  to  o].ierate  the  interrupting  valve.  Seen 
from  above.  The  framework  is  made  of  gaf,  pipe  and  fittings.  The  cross  on  the  right 
hand  end  of  the  frame  and  the  two  tees  on  the  left  end  are  bored  out  to  rotate  on  the 
end  bars.  Thus  the  two  hinges  are  formed.  This  valve  operating  device  can  also  be 
used  in  laboratories  where  compressed  air  from  the  power  plant  is  supplied  to  the  build- 
ings. Hanzlik  has  recently  described  a  multiple  pump  system  for  artificial  respiration. 
(See  Journal  of  Laboratory  and  Clinical  Medicine,  1916,  i,  688.)  Several  artificial  res- 
piration machines  using  bellozvs,  etc.,  are  on  the  market.  For  student  purposes  these 
should  be   avoided. 


Fig.   362. — Lever  gate  valve    (Lukenhcimer,   "Handy  valve").      These  are   stock  valves 
and  cost  from  40  cents  to   $1.00.     They   are  able  to  withstand   125   pounds  steam  pressure. 


Open 


ARTIFICIAL    RESPIRATION    MACHINE 

From  fdnk 
■Closed — M         b. 


475 


/ \ 


\ 


Open 


Closed 


c/o.#^-Jr'°'"""'i^^J^c 


Pump 


Negafii/e  pressure         Positive  pressure 

Fig.    363. — Diagram   shov/ing  the   method   of  operation   of   the   lever   gate   reversing   valves. 

Reversing  valves  {Lever gate  vdlves) 
Worm  gears 
Tube  to  operating  tables 

■Interrupting  valve 


Faucet  for 
constant 
pressure  or 
vacuum 


Gauges 


Cone  pulley 

Round  belt 
{Interctiangesble) 

Cone  pulley 
Air  pump 


^y  Connection 
for  power 


Fig  364. — Portable  artificial  respiration  machine.  Based  on  the  principles  illustrated 
in  Fig  360  There  are  several  varieties  of  cheap,  small-sized  rotary  pumps  on  the  market. 
For  a'  small  portable  machine  like  this  for  research  purposes  these  small  pumps  are 
sufficient.  The  special  interrupting  valve  turned  by  worm  gears  is  shown  better  in 
Fig.  366. 


476 


EXPERIMENTAL   PHARMACOLOGY 


every  room  in  the  building.  It  is  important  to  consider  this 
point  in  the  construction  of  new  laboratories. 

Equipment. — The  following  list  of  tools  and  supplies  is  by 
no  means  complete  and  is  intended  merely  to  serve  as  a 
guide  for  those  who  may  care  to  prepare  themselves  to  do 
a  certain  amount  of  shop  work  but  who  may  have  had  no 
previous  training  in  this  field. 

The  author  has  attempted  to  arrange  the  tools,  etc.,  as 
nearly  as  possible  in  the  direct  order  of  their  usefulness 
in  the  laboratory  and  with  reference  to  the  amount  of  money 


From  air  tank 


Trip  pins 


Lever  gate  valve 


Fig.  365. — Special  form  of  interrupting  valve  using  cone  pulleys,  worm  gears,  and 
having  adjustable  trip  pins  to  open  the  lever  gate  valve.  This  valve  can  be  used  where 
compressed  air  is  already  furnished  to  the  laboratory  from  the  power  house.  Air  thus 
supplied  is  often  under  high  pressure  (35  to  70  pounds  or  more).  There  are  special 
reducing  and  regulating  valves  on  the  market  to  reduce  this  pressure  as  it  is  received 
into  a  special  tank  in  the  laboratory.  One  can  use  a  pressure  of  35  pounds  for  artificial 
respiration  if  he  has  a  suitable  interrupting  valve,  one  which  onens  only  a  little  ways 
and  for  a  very  brief  period.  Excessive  quantities  of  air  are  usually  passed  to  the  animal 
but  most  of  this  escapes  at  once  through  the  side  tube  of  the  tracheal  cannula.  This 
slionld  always  be  wide  open  before  artificial  respiration  is  started.  The  instructor  should 
fully   impress   this   on   the   stvidents. 

which  the  department  may  be  able  to  spend  for  the  shop 
equipment.  Thus  the  list  begins  with  those  cheap  hand 
tools  Avhich  are  most  likely  to  be  of  the  greatest  service  in 
laboratories  where  the- funds  are  limited.  As  the  number 
of  tools  multiplies  in  the  list  the  degree  of  usefulness  is 


SHOP    EQUIPMENT 


477 


supposed,  as  nearly  as  possible,  to  keep  pace  with  the 
increased  expense.  In  this  connection,  however,  a  special 
exception  may  be  made  with  reference  to  the  lathe  which  is 
the  most  important  JiigJi-priced  piece  of  machinery  that  the 
shop  can  possess.  Thus  if  the  funds  permit  the  purchase 
of  a  lathe  at  all  this  is  perhaps  best  done  immediately 


Detail  of  valve 
construction 

Axle 


Worm  gear  wheel 
fixed  to  inner 
rotating  tube 


yOuflet   tube 

\  .Outer  fixed  tube 

II  _^  Inner,  rotating  tube 


Wastier  flush 
with  standard, 
not  moveable 

tube 


Fig.  366. — Special  interrupting  valve  driven  by  a  small  (1/10  horse  power)  motor. 
The  details  of  the  construction  of  the  valve  are  shown  in  the  upper  part  of  the  illustra- 
tion. This  valve  is  essentially  like  one  devised  by  Cannon,  Martin  and  Mendenhall. 
Gates  has  also  used  a  principle  like  this  in  connection  with  a  pump  and  motor  combined  in 
one  apparatus.  A  valve  of  this  form  should  be  used  close  to  the  animal,  since  if  the  air 
is  piped  a  long  distance  the  slow  turning  on  and  off  of  the  air  permits  compression  in  the 
tubes  and  a  prolonged,  wave-like  blowing  at  the   outlet  faucets. 

after  the  first  thirty  items  in  the  list  have  been  pro^dded 
for.  On  the  other  hand  if  a  lathe  cannot  be  bought  then  the 
items  may  very  well  be  bought  in  approximately  the  order 
in  which  they  appear  in  the  list.  It  is  to  be  noted,  of  course, 
that  each  mechanic  will  have  manv  small  items  to  add  to 


478 


EXPERIMEISTTAL   PHARMACOLOGY 


the  list,  and  these  items — mainly  special  forms  of  hand 
tools,  attachments,  etc.,  and  special  supplies — will  vary 
according  to  the  training  which  the  mechanic  has  had  and 
with  reference  to  the  special  work  which  the  department 


Fig.    367. — A    motor    driven    long    paper    kymograph    constructed    mainly    of    gas    pipe    and 

fittings. 


may  want  done.  A  few  (approximate)  prices  are  indicated 
in  the  list  for  items  on  which  errors  are  especially  liable  to 
be  made  in  purchasing  or  for  articles  of  great  use  in  the 
shop. 


SHOP   EQUIPMENT 


479 


List  of  Equipment. 

1.  Pliers  (5  inch  flat-nosed,  9  or  10  inch  flat-nosed,  5  inch  end  cuttino). 

2.  Screw  drivers   (small,  20  cents,  and  large,  30  cents;  Yankee,  $1.50). 

3.  Files  (8  inch  flat,  4,  6,  10,  12  inch  flat,  6,  4,  8,  10,  12  inch  round,  square 
and  three  cornered). 

Knife  edge  files,  wood  files  and  rasps  should  be  bought  if  possible. 

4.  Hammers  (claw  hammer,  50  cents;  medium  sized  riveting,  50  cents).    A 
hatchet   (50  cents)  is  desirable. 

5.  Small  vise   ($1.75).     The  jaws  should  open  parallel,  not  like  a  pair  of 
pliers. 


-Inferchanqedble  pulleys 


Idler  pulley 


Slidinq  aUachmenf 
for  Tension  sprinq 


Flan  of  btlfsr 

pulleys 


Fig.  368. — Detailed  view  of  one  plan  of  construction  of  the  speed  regulating  device 
for  the  kymograph  shown  in  Fig.  367.  The  arrangement  of  the  speed  regulation,  depends 
largely  on  the  speed  of  the  motor,  and  hence  different  gears  must  be  used  for  different 
motors. 


6.  Tinner's  snips  (6  inch,  50  cents;  large  size,  $1.25). 

7.  Hand  saw  (24  to  26  inch,  $1.00  to  $1.50). 

8.  Hack  saw,  8  to  12  inch  adjustable  ($1.00)  and  blades  (10  and  12  inch, 
fine  teeth,  60  cents  per  dozen). 

9.  Hand  drill  (Fig.  370,  $2.50)  and  several  dozen  twist  drills.  These  run 
in  sizes  from  No.  60  (a  little  less  than  3/64  inch  in  diameter)  to  No.  1 
(a  little  less  than  1/4  inch  in  diameter).  Drills  larger  than  No.  1  are 
usually  indicated  in  inches,  the  diameter  increasing  1/64  inch  for  each 
succeeding  size.     A  good  supply  of  drills  should  be  kept  on  hand.     The 


480 


EXPERIMENTAL   PHARMACOLOGY 


10. 
11. 


small  sizes  cost  about  10  cents  apiece,  the  larger  sizes  up  to  1/2  inch 
average  20  cents  to  25  cents  apiece.  Very  fine  (jeweler's)  twist  drills 
may  also  be  needed  for  special  work. 

Nails  (wire).  1  or  2  pounds  of  each  size — about  6  or  8  sizes  are  needed. 
Brass.  A  good  supply  of  this  should  be  available  since  a  great  many 
pieces  of  apparatus  can  be  made  from  this  metal.     In  large  cities  brass 


Fig.  369. — Another  form  of  motor  driven  long  paper  kymograph.     (For  detailed  description, 
see  Journal   of   Laboratory  and   Clinical   Medicine,    1917,   ii,  p.    424.) 


can  often  be  bought  as  needed,  but  in  small  towns  a  stock  should  be 
kept  on  hand.  The  tubing  varies  in  size  from  about  1/32  inch  up  to  4 
or  5  inches.  In  some  places  even  larger  sizes  can  be  obtained.  The  wall 
thickness  is  usually  about  1/32  inch  but  other  sizes  are  available.  The 
1/8,  3/16,  1/4,  3/8,  1/2  and  1  inch  sizes  are  most  used  in  the  laboratory 
(especially  the  1/4  inch  size).  The  cost  varies  from  about  50  cents  to 
60  cents  per  pound  for  the  larger  sizes,  much  higher  for  the  very  small 
sizes  (1/16  inch,  etc.).     Round  brass  rod  from  1/8  inch  up  to  1/2  inch 


SHOP    EQUIPMENT 


481 


Fig.   370. — Hand  drill.      Should  hold   drills   from  zero   up   to    Jg    inch  in   diameter. 


482 


EXPERIMENTAL   PHARMACOLOGY 


in  diameter  is  needed  in  abundance.  Larger  sizes  up  to  1  or  2  inches 
are  especially  required  if  lathe  work  is  done.  The  1/8,  3/16,  and  1/4 
inch  sizes  are  used  most  (these  are  the  least  expensive).  The  price  now 
averages  about  50  cents  per  pound.  Square  brass  rod  can  be  bought 
approximately  the  same  as  the  round  (3/16  and  1/4  inch  most  used). 
Hexagon  rods  and  sawed  rods  are  also  available.  Sheet  brass  is  made 
in  thicknesses  varying  from  about  that  of  a  very  thin  sheet  of  paper  up 


Fig.    371. — Blast   lamp.      (Buffalo   Dental    Mfg.    Co.,    Buffalo,   N.   Y.) 


to  1/2  inch  or  more.  It  is  often  available  only  in  rolls  one  foot  in  width 
but  larger  firms  have  rolls  varying  in  size  from  perhaps  1/2  or  1  inch  up 
to  12  inches.  Sheet  brass  is  of  the  greatest  use  in  the  laboratory  not 
only  for  repairing  or  making  regular  student  apparatus  but  especially 
for  experimental  work  and  research.  The  most  used  thicknesses  are 
approximately  1/64,  1/32,  3/64  and  1/16  inch.  A  small  supply  of  1/8 
and  1/4  inch  (and  even  3/8  and  1/2)  brass  plate  is  also  exceedingly 
desirable.    Spring  brass  wire  (Nos.  14,  16,  18)  should  also  be  in  stock. 


SHOP    EQUIPMENT 


483 


12.  Blast  lamp,  (Fig.  371,  $4.50)  and  foot  bellows  (Fig.  359,  $5.00)  or 
compressed  air  aiid  tubing.  These  are  mainly  used  for  soldering  (or 
brazing)  and  are  exceedingly  useful.  If  no  gas  supply  is  available  an 
alcohol  lamp  (20  cents)  and  a  small  mouth  blowpipe  (20  cents)  may  be 
used  for  soldering  many  small  articles. 

13.  Solder  and  soldering  acid.  Solder  is  best  obtained  in  the  form  of  a 
heavy  coiled  wire  about  1/8  inch  in  diameter  (string  solder).  This  form 
is  especially  adapted  for  soldering  with  a  blast  lamp  (which  is  by  far 
the  best  method  for  this  kind  of  work).    Soldering  acid  is  made  by  put- 


„.  ^'g-  ^Ir-~^,^}^^^^  °f  'he  mechanical  construction  of  the  adjustable  tambour  shown  in 
i-ig.  14.  One-half  natural  size.  It  is  recommended  that  all  laboratories  which  have  suffi- 
cient shop  facilities  make  up  at  least  a  few  such  tambours  as  this  for  recording  special 
results  where  large  volume  changes  in  the  tambour  are  required.  Upper  picture,  seen  from 
aoove;  middle  picture,  seen  from  the  side;  the  two  lower  pictures,  the  smallest  and  largest 
Umbour  bowls.  All  parts  made  of  brass.  Thin  sheet  aluminum  writing  points  are  used. 
Ihese  may  be  cut  on  a  hard  board  from  thin  sheet  aluminum  with  a  penknife  and  a  metal 


ting  about  2  or  3  ounces  of  hydrochloric  acid  in  a  6  or  S  ounce  wide- 
mouthed  bottle  and  dropping  in  more  granulated  zinc  than  the  acid  can 
dissolve.  The  bottle  is  placed  in  a  hood  so  long  as  fumes  are  given  off 
from  the  mixture.  A  glass  tube  (8  or  10  inches  long)  is  placed  in  the 
bottle  to  be  used  as  a  pipette  for  placing  the  acid  on  the  articles  to  be 
soldered. 


484 


EXPERIMENTAL   PHARMACOLOGY 


The  above  tools  and  supplies  are  sufficient  for  the  making 
of  most  forms  of  oncometers,  heart  levers,  simple  muscle 
levers,  plethysmographs,  simple  forms  of  tambours, 
T-tubes,  tracheal  or  arterial  cannulas,  frog  clips,  mercury 


^gin  Stopper 
glued  to 
diaphragm 


Metal  tube  for  support  and 
for  connection  to  rubber  tube 


Aluminum 
writing  lever 

Elastic  rubber 
diaphragm 


Fig.  373. — A  cheap  form  of  large  bowled  tambour  made  from  a  nickel  plated  metal 
tumbler  holder  bought  in  a  ten  cent  store.  The  stem  of  the  holder  was  filed  off.  a  hole 
was  punched  in  the  side  of  the  "bowl"  and  a  yi  inch  brass  tube  7  inches  long  was  soldered 
into  the  hole.  The  "bowl"  had  a  round  flange  at  the  rim  over  which  the  rubber  mem- 
brane was  tied.  A  cork  attached  with  mucilage  to  the  membrane  carries  the  writing 
point.  The  brass  tube  is  connected  to  the  receiving  apparatus  by  rubber  tubing.  Many 
small  vessels  can  be  found  in  ten  cent  stores  from  which  tambours,  cardiometers,  etc., 
can  thus  be  cheaply  constructed.     Soldering  is  a  great  aid  in  this  work. 


Fig.  374. — Method  of  tying  the  head  of  a  small  screw  into  a  rubber  membrane  to 
be  used  over  the  end  of  a  stethograph  drum.  No  opening  should  be  made  in  the  rubber 
dam.  Dental  dam,  obtainable  from  dental  supply  companies,  is  recommended  for  stetho- 
graphs,  tambours,  etc.  At  S,  is  shown  a  screw  with  a  small  ring  soldered  on  to  the  end  to 
which  the  string  is  tied. 


manometers,  operating  boards,  etc.,  and  for  doing  a  great 
variety  of  repair  Avork,  electric  wiring,  etc. 

14.  Oil  can  (15  cents  to  $1.25)  and  1  gallon  of  machine  oil. 

15.  Copper  wire,  plain  (Nos.  14,  16,  18),  iron  wire,  plain  (No.  18).  These 
are  often  used  for  holding  pieces  of  apparatus  together  until  the  parts 
can  be  soldered. 

16.  One  jack  plane.  (A  smoothing  plane  and  a  block  plane  are  also  de- 
sirable.) 


SHOP    EQUIPMENT 


485 


17.  A  work  bench  for  wood  and  two  bench  hooks.  The  work  bench  should 
have  two  wood  vises.  (Best  obtained  from  Sears,  Eoebuck  and  Com- 
pany, Chicago.) 

18.  One  brace  and  set  of  wood  bits  (6  to  12  in  number).  Two  screw  head 
counter  sinks,  one  for  wood,  the  other  for  metal  and  to  be  used  in  a 
brace,  are  also  desirable. 

19.  Try  square. 

20.  Iron  carpenter's  square  (18x24  or  12x18  inches). 

21.  A  small  anvil  ($2.00).  A  heavy  anvil  should  also  be  provided  and  is 
required  for  the  heavier  shop  work  ($5.00). 

22.  Small  stock  and  dies  for  machine  threads  ($4.00  to  $7.00).  Several 
extra  sets  of  dies  and  about  20  taps  should  be  bought.  The  most  used 
sizes  are  4/36,  8/32,  3/48,  2/56,  14/20,  12/24,  but  several  extra  taps  of 
larger  size  should  be  in  stock  since  machine  screws  can  be  easily  pur- 
chased to  tit  holes  threaded  with  these  taps.  (If  heavy  work  is  to  be 
done  a  blacksmith's  stock  and  dies  should  be  purchased.) 

23.  Wood  screws,  5  or  6  sizes,  both  with  flat  heads  and  with  round  heads. 
An  assortment  of  small-sized  wood  bolts  should  be  in  stock. 

24.  Machine  screws.  These  vary  in  size,  length  and  style  of  the  head.  The 
heads  are  either  round,  tlat  or  filister,  and  each  style  is  often  needed. 
The  1/8,  1/4,  and  1/2  inch  lengths  are  most  used,  but  longer  lengdiS:  espe- 
cially of  the  larger  sized  screws  should  be  in  stock.  The  diameters  and 
threads  most  used  are  4/36,  8/32,  3/48,  2/56,  14/20,  12/24,  but  several 
extra  sizes  of  larger  screws  should  be  in  stock.  Brass  screws  can  be 
purchased  of  practically  the  same  sizes  and  styles  as  the  iron  ones  but 
dealers  often  do  not  carry  these  in  stock. 

25.  Scratch  awl. 

26.  Monkey  wrench  (6  inch). 

27.  Fish  tail  burner.     This  is  also  needed  for  smoking  drums. 

28.  Punch  for  metal  (or  sharp  nail  set)  and  cold  chisel. 

29.  Hand  bracket  saw  and  blades  (for  metal). 

30.  Heavy  end  cutting  pliers.  These  should  be  large  enough  to  readily  cut 
in  two  quarter-inch  iron  wire. 

A  marked  eliange  in  the  scope  and  character  of  the  work 
Avhich  can  he  done  in  the  shop  Avill  he  introduced  hy  the 
purchase  of  the  remaining  items  in  the  list. 

31.  Pipe  stock  and  dies — about  6  sets  of  dies  and  taps,  but  several  more 
sets  are  greatly  to  be  desired.     The  common  sizes  are  1/2,  3/8,  1/4,  3/4, 

.  1/8,  and  1  inch.  The  right  hand  taps  for  these  may  be  omitted  but  are 
desirable.  The  corresponding  left  hand  dies  and  taps  are  often  of  great 
use.  Extra  dies  (and  taps)  are  also  desirable  if  work  with  large  size 
piping  is  to  be  done. 

32.  A  great  many  pipe  fittings,  tees,  elbows,  crosses,  nipples,  unions,  thimbles, 
side  outlet  eibows,  side  outlet  tees,  side  outlet  crosses,  return  bends,  re- 
ducers, faucets,  valves,  street  elbows,  45°  elbows,  flanges,  etc.,  etc.,  are 
easily  available  from  dealers  in  plumber 's  and  gas  fitter 's  supplies. 
These  fittings  are  cheap,  strong  and  durable.  Generally  one  will  need 
to  buv  a  supplv  of  gas  piping  (1/8,  1/4,  3/8,  1/2,  3/4,  or  1  inch,  etc., 


486 


EXPERIMEK^TAL   PHARMACOLOGY 


in  size)  to  go  with  the  fittings.  Many  of  these  fittings  (and  piping)  can 
be  bought  in  brass  but  at  considerably  higher  prices.  All  stock  -fittings 
have  right  hand  threads  cut  in  them  but  a  left  hand  tap  can  be  run  down 
into  these  fittings  (best  done  in  a  lathe)  and  left  hand  threads  thus  cut 
(across  the  right  hand  ones.  Thus  one  can  frame  up  a  square  with  gas 
piping  using  regular  fittings  but  the  left  hand  joints  may  not  be  sufii- 


Bushing 


-Some   of  the   more   common   types   of  gas   pipe   fittings.      Special   forms   can   be 
found  in  catalogues  of  plumbers'  and  gas  fitter's  supply  houses. 


ciently  tight  to  hold  water  or  steam.  (See  Fig.  375.)  If  one  knows 
exactly  what  fittings,  etc.,  are  available  he  can  often  make  out  an  or- 
der for  exactly  the  pieces  which  he  may  need  for  an  extensive  piece  of 
work  and  purchase  from  a  gas  fitter's  or  plurnber's  supply  house  the 
fittings,  piping,  etc.,  all  completely  threaded  and  ready  to  screw  together 
with  a  wrench.  The  author  has  sometimes  been  surprised  at  the  cheap- 
ness with  which  such  equipment  may  be  purchased.     This  procedure  is 


SHOP   EQUIPMENT 


487 


especially  liable  to  be  of  use  to  those  who  may  care  to  install  an  artificial 
respiration  system  in  an  old  laboratory  or  to  those  who  have  but  few 
shop  facilities  of  their  own.  It  is  advisable  to  obtain  a  catalogue  of 
gas  fitter's  or  plumber's  supplies,  e.g.,  that  of  the  Crane  Company,  836 
South  Michigan  Avenue,  Chicago. 

Large  vise    ($9.50)    the   jaws   should   open  parallel   and   there  is   little 
danger  of  getting  too  large  a  vise.     One  with  41/2  inch  jaws  opening 
seven  or  eight  inches  is  advisable.     (A  satisfactory  vise  is  the  No.  20, 
made  by  the  Prentiss  Vise  Company,  New  York.) 
Stillson  wrenches,  6  inch  and  10  inch. 

35.  Pipe  cutter. 

36.  Mitre  box  and  saw  ($10.00  to  $12.00). 

37.  Heavy   hammer    (Adze-eye,    ball   pein,   machinist's    hammer,   1    pound, 
$1.35). 


33 


34 


Fig.   376. — Small  electric   heater.     Useful   for  dissolving  drugs,   etc. 


38.  Supply  of  iron  rods  (round,  square,  flat  strips,  etc.)  and  angle-  and  T- 
irom  These  iron  rods,  strips,  T-iron,  angle  iron,  etc.,  are  not  very 
expensive  and  can  often  be  used  (especially  the  smaller  sizes)  instead 
of  brass. 

39.  Hand  emery  wheel  ($5.00).  If  a  power  emery  Avheel  (which  is  greatly 
to  be  preferred)  is  obtainable  then  the  hand  emery  wheel  can  be  omitted. 
Burnishing  and  polishing  can  usually  be  done  by  placing  burnishing 
wheels  on  the  same  head  that  holds  the  (power)  emery  wheel. 

40.  Calipers,  (2  sets,  3  inch  and  5  inch — inside  calipers,  3  inch,  are  also 
needed). 

41.  Wire  gauge. 

42.  Screw  thread  gauges  (2  are  generally  necessary  to  get  a  full  range  of 
different  thread  sizes). 

43.  Drill  gauge. 


488  EXPERIMENTAL   PHARMACOLOGY 

44.  Turning  lathe  for  metal.  There  are  many  varieties  of  these  lathes  on 
the  market,  varying  in  price  from  about  $50.00  to  approximately  $1000.00 
for  such  sizes  as  might  be  bought  by  the  department.  It  is  strongly 
advisable  not  to  buy  a  low-priced,  cheaply  constructed  lathe.  The  author 
has  found  the  Star  lathes  (Seneca  Falls  Manufacturing  Company,  Seneca 
Falls,  New  York)  very  satisfactory.  Small  lathes  are  to  be  avoided, 
and  the  16  inch  (or  13  inch)  swing  size  is  better  than  the  11  inch,  which 
in  turn  is  to  be  preferred  rather  than  the  9  inch  size.  The  lathe  should 
have  automatic  longitudinal  and  cross  feeds,  should  be  able  to  cut  a 
large  range  of  threads  and  should  be  so  constructed  that  a  full  set  of 
attachments,  such  as  a  taper  cutting  device,  a  milling  device,  etc.,  can  be 
readily  attached  at  any  later  date.  Exposed  gear  wheels  around  the 
head  stock  are  to  be  avoided  and  especial  care  should  be  taken  to  see 
that  changes  from  one  thread  to  another  in,  the  thread-cutting  device 
can  be  made  quickly  and  easily.  In  the  best  lathes  this  is  largely  done 
by  simply  shifting  levers,  in  the  cheaper  lathes  an  unwieldy  number  of 
separate  and  independent  iron  gear  wheels  must  be  taken  oif  and  re- 
placed by  others  to  produce  most  or  all  of  the  shifts  in  threads. 

It  is  very  convenient  to  have  a  motor-driven  lathe,  i.e.,  one  with  the 
driving-motor  attached  directly  to  the  lathe.  This  makes  the  lathe  en- 
tirely independent  of  the  other  machinery  in  the  shop,  but  it  is  slightly 
more  expensive  (if  several  other  motor-driven  machines  are  used)  than  is 
the  arrangement  whereby  one  motor  is  used  to  drive  a  power  shaft  from 
which  all  the  machinery  in  the  shop  is  actuated.  This  also  applies  to 
most  of  the  other  motor-driven  machines. 

A  few  attachments  are  usually  sold  with  the  lathe  but 
many  others  are  always  needed.  A  full  set  of  turning  tools 
should  be  secured,  and  the  following  are  needed : 

4(3.  Three  chucks — Cushman,  universal,  one  as  large  as  the  lathe  will  carry, 
one  21/^  inches  and  one  about  4  inches  in  diameter.  Each  chuck  should 
have  2  sets  of  jaws.  Chucks  are  very  expensive  and  if  only  1  can  be 
bought  this  should  be  about  4  inches  in  diameter.  In  addition  a  Jacob's 
drill  chuck  (holding  drills  at  least  up  to  ^2  inch  in  diameter)  should 
be  purchased.     This  chuck  should  be  fitted  to  the  lathe. 

47.  Armstrong  cut-off  tool  (and  bits),  Armstrong  boring-out  tool,  and  a 
threading  tool. 

48.  Crotch  center,  screw  face  plate,  tail  face  plate,  two  lathe  dogs,  and  a 
nurling  tool. 

49.  A  power-driven  drill  press.  It  is  convenient  to  have  the  motor  attached 
to  the  drill  press  but  this  is  more  expensive  than  the  power  shaft  ar- 
rangement. The  drill  press  should  have  Mnd  feed  (and  power  feed 
also  if  possible)  and  should  drill  to  the  center  of  at  least  a  12  or  14 
inch  circle  (or  larger  if  possible). 

50.  A  wood  lathe.  (Burnishing,  buflfing  and  polishing  may  also  be  done  by 
especially  attaching  buffing  wheels  to  the  wood  lathe.) 

51.  A  shaper  (planer)  for  metal. 

52.  A  power  hack  saw  ($25.00). 

53.  A  milling  machine  ($500.00). 

54.  If  much  wood  work  is  done  a  v/ood  former  ($20.00)  may  also  be  useful. 


SOLDERING  489 

To  this  list  every  mechanician  will  want  to  add  various 
hand  tools,  etc.  The  expense  of  these,  however,  will  not, 
as  a  rule,  be  very  great  at  any  one  time,  for  such  equip- 
ment is  usually  needed  for  special  pieces  of  w^ork,  and  the 
tools  required  can  be  bought  from  time  to  time  as  the  funds 
are  available. 

Mechanical  Procedures. 

A  few  paragraphs  may  be  devoted  to  some  of  the  most 
elementary  and  useful  mechanical  procedures  which  may 
be  carried  out  in  the  shop.  The  first  of  these  is  soldering. 
The  metals  best  suited  to  this  work  are  brass,  copper, 
tinned  iron  and  wa^ought  iron.  Cast  iron  is  scarcely  suit- 
able. Galvanized  (sheet)  iron  is  soldered  readily.  The 
process  is  exceedingly  simple,  and  easil}^  carried  out  if  the 
parts  to  be  soldered  together  are  not  very  complicated. 
The  most  difficult  feature  of  the  process  is  to  hold  the  va- 
rious pieces  in  the  proper  position  until  the  solder  can  be 
applied.  This  is  usually  best  done  either  by  tying  the 
pieces  together  in  the  right  position  with  wire  (copper  or 
soft  iron,  smooth,  jSFo.  16  or  18)  or  by  fastening  the  pieces 
down  to  a  board  or  block  of  wood  in  the  proper  position 
by  means  of  small  nails  driven  into  the  wood. 

A  blast  lamp  burning  gas  and  supplied  with  compressed 
air  (easily  obtained  from  a  rotary  pump  such  as  should  be 
used  for  artificial  respiration)  is  the  best  method  to  be 
used  for  melting  the  solder.  A  foot  bellows  may  be  used 
to  supply  the  air.  A  blast  lamp  exactly  like  the  one  shown 
in  Fig.  371  should  be  provided. 

Small  articles  can  be  soldered  with  a  spirit  lamp  and 
mouth  bloA\Tpipe  but  this  is  both  tedious  and  tiresome  ex- 
cept for  the  very  smallest  articles.  Tinners  and  some  me- 
chanics use  a  soldering  copper  but  this  is  a  crude  method 
and  often  entirely  unsuited  for  much  of  the  work  required 
in  making  ordinary  pieces  of  apparatus.  But  a  soldering 
copper  is  of  service  in  the  soldering  of  aluminum  for  which 


490 


EXPEEIMEXTAL   PHARMACOLOGY 


special  aluminuin  solder  must  be  bought.  No  acid  is  used 
in  aluminum  soldering  but  the  scraped  metal  surfaces  are 
heated  and  the  aluminum  solder  is  rubbed  on  the  proper 
places  with  the  (very)  hot  soldering  copper.  The  author 
has  not  found  a  blast  lamp  very  satisfactory  for  aluminum 
soldering. 

For  ordinary  soldering  on  brass,  etc.,  a  small  flame  from 
the  blast  lamp  is  best.  Fig.  377  shows  the  method  of  ap- 
plying the  flames  in  making  a  brass  T-tube  or  tracheal 


Fig.   m. — Method  of  preparing  two  pieces   of  brass  tubing  for  making  a  tracheal  cannula, 
and  the   process  used  for  holding  and   soldering  the  pieces  together. 

cannula.  But  soft  solder  mil  not  stick  to  the  brass,  etc., 
unless  a  soldering  acid  is  used.  This  soldering  acid  or 
fluid  is  made  by  placing  granulated  zinc  in  hydrochloric 
acid  and  allo^^ing  the  acid  to  dissolve  all  of  the  metal  pos- 
sible. An  excess  of  zinc  should  be  left  in  the  bottom  of  the 
bottle.  The  acid  is  applied,  to  the  article  by  means  of  a 
glass  tube  used  as  a  pipette.  Fig.  377  also  shows  the  two 
pieces  of  brass  tubing  Avhich  have  been  filed  (or  sawed)  off 
of  a  long  brass  tube.  .These  two  short  pieces  are  filed  with 
a  round  file  as  shown  in  the  illustration,  an  opening  being 


SOLDERIJfG 


491 


made  near  the  middle  of  the  longer  piece  b}^  cutting  into 
the  side  of  the  tube  with  the  round  file,  while  one  end  of 
the  short  piece  is  cut  in  circular!}^  to  fit  over  the  opening 
in  the  longer  piece.  These  pieces  are  fitted  together  and 
then  fastened  down  to  a  small  block  of  wood  by  a  few  small 
nails.  The  joint  is  then  heated  fairly  hot  (to  remove  grease, 
etc.)  with  the  flame  and  then  a  feAV  drops  of  the  acid  are 
applied  to  the  joint.  This  acid  is  at  once  vaporized  by  the 
heated  metal  but  in  this  process  the  acid  penetrates  every 
portion  of  the  joint.  The  flame  is  uoav  reapplied  and  at  the 
same  time  the  end  of  a  piece  of  wire  solder  (string  solder)  is 
placed  on  the  joint.  The  solder  melts  quickly  and  runs  into 
every  part  of  the  joint.  Beginners  usually  get  on  too 
much  solder.  Only  a  small  amount  is  needed  as  a  rule 
and  more  ma^^  even  do  harm.  The  flame  can  be  directed 
beneath  the  tube  to  insure  soldering  of  the  lower  part  of 
the  joint.  More  acid  can  be  applied  if  the  solder  does  not 
stick  at  the  first  application.  As  soon  as  the  joint  is  seen 
to  be  run  full  of  solder  the  flame  is  removed  and  no  more 
solder  is  applied.  Cold  water  is  poured  over  the  tubes  and 
the  soldering  is  complete.  The  cannula  is  now  removed 
from  the  board  and  a  fine  rasp  or  wood  file  (not  a  fine  file 
for  metal)  is  used  to  file  away  any  excess  lumps  of  solder 
and  make  the  joint  smooth  and  regular. 

This  operation  is  typical  for  most  of  the  soldering  re- 
quired in  the  laboratory.  But  a  further  complication  arises 
if  two  pieces  are  to  be  soldered  together  close  to  a  joint 
which  has  already  been  soldered.  In  this  case  heat  from 
the  flame  may  melt  apart  the  first  joint  while  the  solder  is 
being  applied  to  the  second.  This  can  usually  be  avoided 
by  wrapping  the  first  joint  Avith  wet  cotton  or  a  wet  cloth 
(probably  tied  on  with  soft  copper  wire)  while  the  second 
joint  is  soldered. 

The  making  of  oncometers  for  the  kidney,  spleen  or  in- 
testinal loop,  etc.,  can  be  readily  done  by  simply  cutting 
out  pieces  of  sheet  brass  into  the  proper  shape  and  then 


492 


EXPEEIMENTAL   PHARMACOLOGY 


soldering  the  edges  together  as  above  described.  The 
method  is  quite  similar  to  that  which  one  would  employ  if 
he  desired  to  make  a  pasteboard  case  to  cover  an  irregularly 
shaped  object  such  as  an  ink  bottle.  He  would  simply  cut 
out  pieces  of  the  pasteboard  to  fit  the  various  surfaces  of 


Fig.    378. — First   step   in   the    making   of   small    "straight"    glass    cannulas. 


Fig.   379. — The  "shoulders"  of  the  cannulas  are  carefully  heated  in   a  needle-pointed  flame 
and    drawn   out   a  little   to   form   the   "necks"   on   the   two    cannulas. 


Fig.    380. — The    points    of   the    cannulas    are    broken    off    at    the    file    marks    and    the    large 
end  of  each  cannula  is  rounded  in  the  flame. 

the  bottle,  bending  those  which  covered  curved  areas,  and 
then  he  would  fasten  the  edges  together  with  glue  or 
mucilage. 

Pieces  of  iron  may  be  brazed  by  heating  them  red  hot, 
covering  the  areas  to  be  brazed  with  powdered  borax 
(which  promptly  melts)  and  then  putting  small  pieces  of 


GLASS    BLOWING  493 

"brass  on  the  joint  while  applying  a  very  intense  blast  lamp 
flame.  The  brass  melts  and  passes  into  all  the  crevices 
between  the  adjoining  pieces  of  iron.  When  the  parts  are 
cooled  a  very  firm  joint  should  be  formed. 

Glass  Blowing. — Only  two  of  the  most  common  operations 
need  be  mentioned  here,  for  the  making  of  complicated 
articles  of  glass  requires  great  skill  and  long  practice  and 
training.  It  is,  however,  often  almost  imperative  for  the 
instructor  or  mechanic  to  be  able  to  make  a  few  things  from 
glass  tubing.  These  articles  are  usually  cannulas,  and  tubes 
which  are  bent  in  various  directions.  Very  fine  pointed 
cannulas  are  so  easily  broken  and  are  so  frequently  needed 
that  it  is  a  matter  of  special  importance  for  the  simpler 
forms  to  be  made  in  the  laboratory.  Figs.  378,  379,  and  380 
show  essentially  the  processes  involved.  Very  fine  can- 
nulas, as  those  needed  for  Wharton's  duct  or  the  thoracic 
duct,  should  be  made  of  small  tubing  (about  3/16  inch  out- 
side diameter).  The  glass  is  heated  up  slowly  at  first  (best 
in  a  smoky  flame)  to  avoid  cracking.  A  very  small  flame 
is  then  used  to  heat  a  short  length  (i/4  to  14  inch)  of  the 
tube.  When  the  glass  softens  (the  tube  is  rotated  con- 
stantly) the  heated  part  is  then  dra^vn  out  for  a  distance  of 
two  or  three  inches,  depending  on  the  size  of  the  point 
desired  for  the  cannula.  The  glass  is  then  allowed  to  cool 
enough  to  harden.  The  flame  is  then  made  exceedingly 
small  and  is  directed  against  one  of  the  "shoulders"  of 
the  drawTi  out  portion  of  the  tube.  The  tube  is  kept  rotating 
and  as  soon  as  the  glass  in  the  "shoulder"  begins  to  be- 
come fairly  soft  it  is  quickly  dra-v\ai  out  a  little  and  a 
"neck"  is  thus  made  for  the  cannula  as  shown  in  Fig.  379. 

The  process  is  repeated  for  the  other  "shoulder"  and  two 
cannulas  are  thus  formed  but  are  held  together  by  a  nar- 
row length  of  the  drawn  out  tubing.  With  the  sharp  corner 
of  a  file  a  scratch  is  made  a  little  beyond  the  point  where  the 
tip  of  each  cannula  should  be.  The  tube  is  snapped  ofi^  at 
each  of  the  scratches  and  then  the  points  of  the  cannulas  are 
carefully  rounded  by  heating  in  a  very  small  yellow  flame. 


494 


EXPERIMENTAL   PHARMACOLOGY 


'^■-T^t^ffe'cW^?^^^^ 


Fig.    381. — Heating  a   ttibe  before   bending.      The  tube   is   constantly   turned   in  the   fingers. 


Fig.  382. — When  the  tube  is  sufficiently  soft  it  is  bent  upward  to  the  desired  angle. 


GLASS    BLOWING 


495 


A  special  form  of  emery  wheel  or  a  file  may  be  used  to 
slant  the  end  of  the  cannula  before  the  point  is  rounded. 
The  danger  here  is  that  the  points  may  be  heated  too  hot 
and  become  sealed  off.  The  outer  edge  of  a  very  small 
yellow  flame  is  employed  for  this  Avork.  Each  cannula  as 
a  Avliole  is  then  cut  off  from  the  main  length  of  tlie  glass 
tube  by  scratching  a  ring  around  the  tube  with  a  file  and 
snapping  the  cannula  off  at  the  ring.  The  rough  ends  thus 
formed  are  rounded  by  heating  gently  in  the  flame  and  the 
cannula  is  made.     It  should  be  cooled  slowly. 


Position  of  ndils 

I  I 


mm 


Board  held  in  me 
or  nailed  to  table 


wire  wrapped  as  shown 
^      by  arrows 


Cut  off  ends  with  ■. 
nippers  after  wire 
is  bent 


No  18  spring  brass  wire 


fjallecif 


Fig.    383. — Process   for   making  frog   clips. 

For  the  purpose  of  bending,  glass  tubes  should  be  heated 
in  the  flame  from  a  fish  tail  burner  (the  tube  is  constantly 
rotated)  as  shown  in  Fig.  381.  As  the  glass  softens  over 
a  sufficient  length  of  the  tube  the  two  ends  of  the  tube  are 
bent  upward  and  brought  to  the  proper  angle  as  sho^^m  in 
Fig.  382.  This  is  tlie  method  used  for  bending  manometer 
tubes,  etc.  The  danger  usually  is  that  not  a  long  enough 
length  of  the  tube  may  be  heated  before  the  bend  is  at- 
tempted. The  bent  tube  should  be  cooled  very  slowly  to 
avoid  cracking. 

Frog  Clips. — These  can  be  made  cheaply  and  easily  by  the 
method  shown  in  Fig.  383.     The  seven  small  nails  driven 


496 


EXPERIMENTAL    PHARMACOLOGY 


into  the  end  of  a  small  board  should  have  their  heads  filed 
off  so  the  bent  wire  clip  can  be  easily  removed. 

Brass  Arterial  Cannulas. — Fig.  384  shows  the  method 
nsed  for  making  small  brass  arterial  cannulas.  A  round 
brass  rod  of  suitable  size  is  held  in  the  lathe  chuck  and 
turned  down  to  the  right  size  and  shape.  After  the  out- 
side of  the  cannula  is  entirely  finished  then  a  very  small 
drill  is  passed  through  the  cannula  (from  the  small  end). 
The  cannula  can  then  be  cut  off  to  the  proper  length  and 
again  placed  in  the  chuck  in  a  reversed  direction  when  a 
larger  drill  can  be  run  dowm  the  large  end  of  the  cannula  to 
near  the  shoulder.    By  this  means  exceedingly  strong  and 


Turned 
br,a5s  cannula 
held  in  laf-he  chuck 


Chuck  in  fail  stock 


Fig.  384. — Method  for  making  very  small  brass  cannulas.      (For  discussion  see  text.) 

small  i3ointed  cannulas  can  be  made.  They  are  much  more 
durable  than  similar  glass  ones  but  hardly  so  satisfactory 
for  most  purposes.  Many  sizes  can,  however,  be  made  and 
since  these  metal  cannulas  can  be  soldered  into  brass  tubes 
in  pairs  or  in  any  other  desired  fashion  they  often  can  be 
used  for  a  variety  of  purposes,  and  also  in  laboratories 
where  similar  glass  cannulas  are  wholly  unobtainable. 

Stands  and  Castings. — Fig.  385,  wliich  shows  a  stand  witli 
a  right-angled  base,  may  be  taken  as  typical  of  a  large 
number  of  articles  which  may  be  secured  cheaply  and  easily 
in  the  laboratory.  This  stand  (which  is  exceedingly  satis- 
factory in  practice)  was  obtained  by  first  making  a  wooden 
pattern  of  the  form  and  dimensions  indicated  in  the  illus- 
tration.    This  pattern  was  then  sent  to  a  foundry  where 


METAL    CASTINGS 


497 


several  dozen  of  the  bases  were  cast  of  iron  (at  a  cost  vary- 
ing between  four  cents  and  ten  cents  per  pound).  The 
three  holes  in  the  top  of  the  base  were  then  bored  and 
threads  were  cut  in  the  holes  so  that  the  rod  could  be 
screwed  into  either  hole  as  desired.  The  rods  were  made 
of  galvanized  iron  pump  rod  7/16  inch  in  diameter.  All 
of  the  metal  work  can  be  done  at  the  average  foundry,  and 
much  more  cheaply  than  such  stands  can  be  obtained  by 


Removable 
supporting  rod 
^  in.  X  2^  in. 


Leg  ii)(i§^7in. 

Fig.  385. — Large  stand  with  L-shaped  base.     The  supporting  rod  can  be  screwed  into  either 
hole.      (For   discussion   see  te.xt. ) 

purchase  in  the  open  market.  It  is  cheaper  (and  often 
quite  satisfactory)  to  have  only  one  hole  bored  in  the  base 
(the  right  hand  hole  as  seen  in  the  picture)  but  to  let  this 
hole  be  bored  entirely  through  the  base.  The  rod  is  then 
driven  into  this  hole  and  riveted  from  the  bottom. 

In  many  places  castings  made  of  brass  or  bronze  are  ob- 
tainable and  are  often  of  especial  value  because  it  is  possible 
to  easily  solder  other  pieces  to  the  castings.  For  research 
purposes  this  is  often  a  very  valuable  possibility. 


498  EXPERIMENTAL   PHARMACOLOGY 

Lacquering". — It  often  happens  that  one  wishes  to  pre- 
serve the  appearance  of  a  new  piece  of  apparatus  and  to 
jjrevent  oxidation  of  the  metaL  For  brass  articles  this  can 
often  be  readily  done  by  lacquering.  A  good  coat  of  lacquer 
is  often  more  satisfactory  than  nickel  plating  for  the  nickel 
is  very  liable  to  corrode  in  the  atmosphere  of  a  laboratory. 

Lacquering  can  onl}^  be  done  satisfactorily  after  the  metal 
has  been  well  burnished  and  polished.  This  is  done  by  means 
of  cloth  (or  felt)  buffiug  wheels  (costing  about  25  to  50 
cents  apiece),  which  are  turned  at  a  high  speed  (2000  or 
more  revolutions  per  minute)  while  the  metal  articles  are 
held  against  the  rotating  edge  of  the  Avheel.  The  buffing 
wheels  can  usually  be  placed  on  the  same  head  as  that  used 
to  turn  the  (power)  emery  wheel.  Or  the  buffing  wheel  may 
be  placed  on  an  arbor  which  can  be  held  in  the  chuck  of  a 
lathe  and  turned  at  the  highest  speed  obtainable  with  the 
lathe.  For  the  first  or  coarse  buffing  a  substance  called 
tripoli  (which  resembles  a  bar  of  soap  into  which  a  large 
amount  of  powdered  pumice  stone  had  been  mixed  while  the 
soap  was  melted)  is  rubbed  on  the  buffing  wheel.  The  metal 
instrument  is  then  brought  against  the  wheel  and  is  quickly 
rubbed  smooth,  and  file  scratches,  etc.,  may  be  completely 
removed  by  grinding  off  the  outer  layers  of  the  metal.  The 
finer  polishing  is  then  finished  on  a  second  (cloth)  wheel 
to  which  a  substance  called  rouge  (resembling  a  very  fine, 
dry,  reddish  bar  of  soap  containing  a  still  finer  powder  of 
pumice  stone)  is  applied.  This  wheel  gives  the  brass  a  very 
high  degree  of  polish  and  the  instrument  should  be  wiped 
off  with  a  clean,  dry  towel  after  this  buffing  is  completed. 

The  best  lacquer  the  author  has  used  was  obtained  from 
the  Kahlbaum  chemical  works  and  was  called  metall  furniss 
(HocJi  gold).  This  lacquer  should  be  diluted  several  times 
with  pure  ethyl  alcohol.  A  very  thin  solution  is  thus  ob- 
tained and  should  be  applied  very  quickly  with  a  wide,  flat 
camel's  hair  brush.  Small  articles  can  best  be  dipped  into 
the  solution.  Drying  -should  occur  very  rapidly  and  it  is 
usually  not  possible  to  overlap  two  separate  coatings  of  the 


LACQUERING  499 

lacquer  witliout  getting  a  very  bad  looking  i3ate]i  Avliere 
the  two  coats  came  together.  This  is  avoided  by  coating 
the  whole  article  quickly  and  completely  at  the  first  appli- 
cation. 

From  this  brief  discussion  the  value  of  shop  facilities, 
especially  to  laboratories  whose  equipment  is  small,  may 
be  readily  appreciated.  A  further  very  important  reason 
for  the  existence  of  a  shop  in  each  laboratory  is  the  stimulus 
which  it  will  serve  to  offer  to  the  members  of  the  staff  to 
carry  out  new  experiments,  and  to  investigate  new  problems 
Avhich  new  apparatus  and  new  facilities  made  available  by 
the  shop  will  create. 


chaptp:;r  ii. 
photography. 

In  all  pharmacological  laboratories  (especially  if  any 
original  work  is  being  done)  circumstances  often  arise  in 
which  it  may  be  desirable  to  do  some  one  or  more  forms  of 
photographic  work.  In  all  laboratories  where  the  expense 
can  be  afforded  the  author  recommends  that  a  dark  room 
and  a  good  photographic  outfit  be  provided. 

The  present  chapter  is  intended  only  to  very  briefly  dis- 
cuss a  few  of  the  more  fundamental  processes  which  may 
be  of  the  widest  applicability  in  the  laboratory.  These  pro- 
cesses involve  particularly  the  routine  production  of  nega- 
tives and  prints,  developing,  fixing,  printing,  etc.,  the  mak- 
ing of  blue-prints,  lantern  slides,  copying,  etc.  A  full  de- 
scription of  the  theory  and  finer  details  of  photographic 
work  is  not  attempted  here  since  those  who  will  most  care  to 
make  use  of  the  suggestions  offered  in  this  chapter  will 
already  have  had  more  or  less  experience  in  photographic 
work,  especially  in  the  making  of  ordinary  photographs  with 
a  hand  camera,  etc. 

For  several  years  the  author  has  used  in  the  laboratory 
an  ordinary  view  camera  (8x10  size).  The  lens  used  with 
the  camera  is  a  Bauscli  and  Lomb,  protar  VII  A,  size  5x7. 
Either  the  front  or  the  back  half  of  the  lens  can  be  used 
separately  and  will  then  cover  a  somewhat  larger  area  on 
the  plate.  This  outfit  has  been  very  satisfactory  for  labora- 
tory purposes,  especially  for  copying  and  lantern  slide  mak- 
ing. There  are  many  forms  of  lenses  and  cameras  on  the 
market,  the  majority  of  which  are  not  suited  for  laboratory 
purposes.  It  is  best  to  buy  these  articles  only  from  well 
established  and  reliable  firms  which  will  supply  outfits 
properly  adapted  for  doing  exactly  the  work  which  the 


PHOTOGPiAPH  rC    EQUIPMENT 


501 


director  of  tlie  laboratory  describes.  This  will  involve  par- 
ticularly a  lens  which  is  capable  of  being  used  to  photograph 
objects  at  very  close  range,  e.g.,  at  a  distance  of  12,  10,  or 
even  6  inches.     This  is  required  in  copying  such  objects  as 


Object  board  movedble 
up  and  down,si'dewise, 
forward,  backward,  or 
thru  a  small  arc,  about 


Fig.  386. — Method  of  arranging  the  camera  and  arc  light  for  copying.  The  pul- 
ley supporting  the  arc  light  should  be  attached  to  the  ceiling.  (Second  hand  arc  lamps 
can  often  be  bought  of  the  Gregory   Electric   Company,   Chicago,   111.) 

printed  pages  (which  is  often  of  great  service  when  one 
wishes  to  keep  an  exact  record  of  an  article  in  a  borrowed 
journal,  etc.)  and  for  making  lantern  slides  of  pictures, 
tables,  charts,  tracings,  etc.,  from  books  or  Imnographic 


502 


EXPEKIMENTAL   PHAEMACOLOGY 


records.     A  cheap  lens  or  one  usually  supplied  with  an 
ordinary  view  camera  will  not  do  this  work. 

The  average  time  required  for  an  exposure  of  a  plate  in 
the  light  of  the  laboratory  (from  9  a.  m.  to  about  2  or  3  p.  m.) 
will  be  about  twenty  to  twenty-five  seconds.    The  plate  is 


Board  attached 
to  ceiling 


Fig.   387. — Method  of  suspending  an  adjustable  arc  light  above  the  operating  table, 
lamp  should  be  2   or   3   feet   above  the  field  of   operation. 


The 


then  taken  into  the  dark  room  and  developed.  For  lantern 
slides  the  negatives  should  be  thoroughly  developed  and 
should  be  considerably  darker  than  is  required  for  making 
ordinary  paper  prints.     If  only  a  small  amount  of  work 


DEVELOPER  FOR  PLATES 


503 


is  to  be  done  it  is  better  to  buy  developer  already  put  up 
in  tubes  or  packages,  one  of  which  is  dissolved  in  the  proper 
amount  of  distilled  water  just  at  the  time  it  is  needed.  And 
this  procedure  is  perhaps  always  advisable  if  sufficient 
funds  are  available.  It  is,  however,  somewhat  cheaper  to 
make  up  stock  solutions  of  developer  to  be  kept  on  hand.  As 
stock  developing  solutions  the  Hammer  Dry  Plate  Company 
recommends  the  follomng: 


Pyro  Developer. 

Solution  No.  1 : 

Pure  water 

16 

oz. 

Sodium  sulphite,  anhydrous 

2V2 

oz. 

Solution  No.  2: 

Pure  water 

16 

oz. 

Sodium  carbonate,  C.P. 

11/4 

oz. 

Solution  No.  3: 

Pure  water 

24 

oz. 

Oxalic  acid 

15 

grains 

Pyro 

1 

oz. 

To  develop  use: 

Pure  water  (winter) 

6 

oz. 

Pure  water   (summer) 

8 

oz. 

No.  1 

% 

oz. 

No.  2 

1/2 

oz. 

No.  3 

% 

oz. 

Use  pure  water,  distilled,  rain  water  filtered  or  river 
water  boiled  and  filtered,  in  mixing  the  solutions.  Keep 
the  solutions  in  tightly  stoppered  bottles.  In  using  crys- 
tals use  twice  the  weight  given.  If  negatives  are  too  strong 
use  more  water,  if  too  weak  or  thin  use  less  water.  If  the 
negatives  have  too  much  of  a  straw  color  use  more  of  No.  1, 
but  if  the  negatives  have  too  blue  a  cast  use  less  of  No.  1. 
All  chemicals  should  be  thoroughly  dissolved  while  mixing 
them.  The  anhydrous  sulphite  and  carbonate  of  sodium  are 
much  to  be  preferred.  Wash  the  plates  well  before  placing 
them  in  the  fixing  bath. 


504 


EXPERIMENTAL    PHARMACOLOGY 


Fig.  388. — Measuring  glass,  graduated  in  ounces. 

Metol  Hydrochinon  Developer. 

Solution  No.  1 : 

Pure  water  80       oz. 

Metol  Va  oz. 

Hydrochinon  Vi  oz. 

Sodium  sulphite,  anhydrous                3       oz. 

Solution  No.  2: 

Pure  water  80       oz. 

Sodium  carbonate,  C.P.        .  2i^  oz. 

To  develop  use: 

Pure  water  2  oz. 

No.  1  1  oz. 

No.  2  1  oz. 

The  metol  nmst  be  thoroughly  dissolved,  then  add  the 
hydrochinon  and  sulphite. 

The  plain  fixing  bath  is  made  as  follows : 


Pure  water 

Sodium  hyposulphite 


16  oz. 
4  oz. 


Negatives  should  be  left  in  this  bath  some  little  time 
after  the  Avhiteness  disappears.  This  bath  must  not  be 
used  after  it  is  discolored. 


LANTERN    SLIDES  505 

After  fixing-  the  negatives  should  be  thoroughly  washed 
and  then  placed  in  a  rack  to  dry. 

A  negative  or  lantern  slide  that  is  too  dark  may  some- 
times be  reduced  (made  lighter)  by  placing  it  for  a  little 
while  in  the  following  solution: 

Solution  No.  1  : 

Potassium  fenieyanide  1  oz. 

Water  16  oz. 
Solution  No.  2: 

Sodium  hyposulphite  1  oz. 

Water  16  oz. 

Dissolve  the  ferricyanide  in  a  dark  bottle  (or  wrap  the 
bottle  in  opaque  paper)  as  it  is  affected  by  the  light.  Re- 
duction should  be  carried  out  in  subdued  light,  never  by  a 
strong  daylight.  Take  a  sufficient  quantity  of  No.  2  to 
cover  the  negative  in  a  tray  and  add  a  small  quantity  of 
No.  1,  then  immerse  the  negative.  Remove  several  times 
during  the  operation  and  wash  off  the  chemicals  to  avoid 
staining.  Wash  thoroughly  after  the  desired  reduction 
has  been  obtained. 

Lantern  slides  if  made  from  negatives  are  printed  in  a 
printing  frame  in  the  same  manner  as  that  in  which  a  print 
is  made.  The  slide  is  then  developed  in  the  same  w^ay  as  a 
negative  is  developed  and  in  the  same  developing  solution. 

It  is  to  be  noted  that  lantern  slide  plates  are  3%x4 
inches  in  dimensions,  i.  e.,  a  quarter  of  an  inch  shorter  than 
the  corresponding  standard  dry  plate  which  is  3i/4x4i4 
inches.  This  size  of  plate  is  used  to  make  the  negatives 
from  Avhich  the  lantern  slides  are  printed. 

It  often  happens  that  in  the  laboratory  lantern  slides  can 
be  made  up  directly  from  the  objects  themselves  without  the 
labor  and  expense  of  making  negatives.  This  is  especially 
true  for  slides  of  black  tracings  such  as  are  made  in  pharma- 
cological experiments.  The  method  is  as  follows :  Kits 
will  generally  have  to  be  used  to  step  the  size  of  the  plate 
holder  do\\m  to  3i/4x4i4  inches.  A  narrow  strip  of  wood 
(about  the  size  of  a  tooth-pick)  is  glued  into  the  inner  edge 


506  EXPERIMEISTTAL    PHARMACOLOGY 

of  each  end  of  the  kit.  This  will  reduce  the  size  of  the  kit 
opening  to  approximately  3i4x4  inches.  The  regular  lan- 
tern slide  plate  is  placed  in  this  opening  and  the  kjaiiograph 
record  is  photographed  directly  onto  the  lantern  slide.  De- 
veloping is  carried  out  exactly  as  with  a  negative  but  the 
image  usually  shows  up  very  quickly  and  over-development 
should  be  carefully  avoided  as  this  gives  dark  areas  over 
part  or  all  of  the  slide.  The  slide  is  developed,  fixed,  Avashed 
and  dried  and  is  then  ready  for  the  mat,  cover  and  binding 
strips. 

It  is  of  particular  importance  to  note  that  lantern  slides 
of  black  kymograph  tracings  should  be  made  before  the 
tracing  is  varnished.  In  this  condition  an  absolutely  dull, 
jet  black  background  is  presented  in  which  the  record  shows 
as  perfectly  clear  white  lines.  This  kind  of  an  object  is 
most  favorable  for  photographing.  The  paper  on  which  the 
records  are  made  should  always  be  smoked  good  and  black. 
From  small  kymographs  the  records  may  conveniently  be 
removed  and  pinned  to  a  copying  stand  as  shown  in  Fig. 
386.  The  most  convenient  form  of  light  for  this  purpose 
is  an  electric  arc  light  which  can  be  raised  or  lowered  to 
suit  the  height  of  the  table,  etc.  The  light  should  hang  just 
over  the  front  part  of  the  camera.  Two  arc  lights  (one  on 
f^ach  side)  or  mercury  vapor  lamps  possess  certain  ad- 
vantages over  the  arrangement  illustrated  but  are  consid- 
erably more  expensive. 

Records  on  large  kymographs  may  readily  be  photo- 
graphed on  to  lantern  slide  plates  while  the  paper  remains 
on  the  drum.  The  camera  is  placed  on  a  tripod  and  focused 
on  the  record  which  may  be  lighted  either  b}^  an  adjustable 
arc  light  or  by  daylight.  The  image  on  the  lantern  slide 
should  be  made  well  within  the  limits  of  the  plate,  a  margin 
of  14  to  1/^  inch  being  left  around  the  border  of  the  plate  for 
the  mat.  Note  that  lantern  slides  are  always  used  in  the 
lantern  with  the  long  dimensions  of  the  slide  placed  hori- 


LANTERK"    SLIDES 


507 


zontally.    Therefore  the  image  must  stand  erect  across  the 
plate. 

Various  forms  of  mats  are  sold  for  lantern  slides.  These 
are  thin  black  paper  sheets  made  the  size  of  the  slide  on  the 
outside  but  have  openings  (round,  oval,  ol)long,  etc.)  of  dif- 
ferent sizes  cut  out  of  the  center.  In  the  completed  slide 
the  picture  is  seen  through  the  opening  and  the  border  of 


Fig.  389. — Adjustable  frame  for  cutting  lantern  slide  mats.     About  two-thirds  natural  size. 

the  image  on  the  screen  is  of  the  same  shape  as  the  opening 
in  the  mat.  It  is  often  convenient  and  more  satisfactory  to 
make  these  mats  by  use  of  a  small  adjustable  frame  (Fig. 
389)  which  is  laid  down  over  the  slide  and  adjusted  to  the 
size  and  shape  of  the  image  desired  for  presentation  on  the 
screen.  The  frame  is  then  set  (by  thumbscrews)  and  placed 
over  a  sheet  of  (black)  paper  (wrapping  j^aper  is  sufficient). 
With  a  penknife  the  opening  is  cut  out  of  the  paper.    The 


508  EXPERIMENTAL    PHARMACOLOGY 

slide  is  now  adjusted  over  the  opening  in  the  paper  and  the 
outer  edges  of  the  paper  are  trimmed  to  fit  the  slide.  The 
mat  is  now  placed  on  the  film  side  of  the  slide  and  a  clear 
glass  cover  is  laid  over  the  mat.  A  paper  binding  strip  is 
cut  into  four  pieces  to  fit  the  edges  of  the  slide  and  are 
moistened  and  stuck  around  the  slide  in  such  a  manner  as 
to  bind  the  two  plates  of  glass  firmly  together  with  the  mat 
between  them.  After  drying  of  the  binding  strips  the  slide 
is  ready  for  the  lantern. 

A  dilute  aqueous  solution  of  eosin  may  be  used  to  stain  a 
slide  a  red  or  pinkish  color.  An  aqueous  solution  of  uranine 
is  used  to  stain  slides  yellow.  In  each  case  the  staining  is 
done  just  after  the  slide  has  been  finished  (i.  e.,  when  thor- 
oughly washed  just  after  being  taken  out  of  the  fixing  bath). 
If  the  slide  has  already  dried  it  must  be  wet  again  before 
it  is  placed  in  the  staining  solution. 

Pictures  in  books,  tables  printed  in  journals,  ordinary 
photographs  of  dissections  or  the  performance  of  experi- 
ments, etc.,  may  often  be  used  to  great  advantage  for  teach- 
ing purposes  if  photographed  and  presented  in  the  form 
of  lantern  slides.  For  copying  of  this  kind  an  adjustable 
stand  of  which  many  forms  have  been  devised  (Fig.  386) 
is  needed. 

Ordinary  prints  are  generally  best  made  on  developing 
papers  of  Avhich  several  varieties  are  on  the  market.  It  is 
preferable  to  buy  the  prepared  tubes  of  developer  (for 
each  kind  of  paper)  for  this  purpose,  but  it  may  be  cheaper 
to  use  a  stock  developer.  The  follomng  is  recommended 
for  ' '  Cyko ' '  paper : 


Developer. 

Avoirdupois 

Metric    ■ 

Pure  water 

40  oz. 

1000  c.c. 

Metol 

15  grains 

1  gram 

Sodium  sulphite   (dried  powder) 

1  oz. 

28  grams 

Hydrochinon 

60  grains 

4  grams 

Sodium  carbonate   (dried  powder) 

%   oz. 

21  grams 

Potassium  bromide  (10%  solution)  40  drops  40  drops 


MAKING    PRINTS  509 

Dissolve  the  cliemicals  in  the  order  named.  While  the 
above  amount  of  bromide  is  usually  sufficient,  it  may  at 
times  be  found  that  in  order  to  produce  clear  whites,  more 
bromide  must  be  added  by  using  a  few  drops  of  the  fol- 


lowing  solution: 

10%  Bromide  Solution. 

Avoirdupois 

Metric 

Potassium  bromide                                               1  oz. 

50  grams 

Water                                                                   9  oz. 

450  c.c. 

Developing  is  carried  out  as  follows : — Put  sufficient  de- 
veloper in  the  tray  to  cover  the  prints  quickly.  Immerse 
the  print  face  up  by  placing  one  edge  under  the  solution  and 
giving  it  a  quick  push  so  as  to  instantly  cover  the  surface. 
Kemove  any  air  bells  with  a  tuft  of  cotton.  Allow  the  print 
to  remain  until  the  image  has  reached  the  desired  depth. 
The  developing  and  fixing  must  be  conducted  in  an  orange 
or  yellow  light  or  very  weak  lamp  light.  If  too  strong  a 
light  is  used  the  whites  will  fog. 

After  developing,  the  prints  should  be  quickly  put  in  the 
fixing  bath.  A  simple  solution  of  sodium  hyposulphite  in 
water  (1  oz.  to  4  oz.)  may  be  used  for  fixing  prints  for 
temporary  uses  but  for  more  satisfactory  work  an  acid 
fixing  bath  made  up  as  follows  is  advised: 

Fixing  Bath. 

Avoirdupois  Metric 

Water  64  oz.  2000  c.c. 

Hyposulphite    of    soda  16  oz.  500  grams 

Dissolve  and  then  add  the  following  acid  hardener : 

Avoirdupois  Metric 

Water  5  oz.  150  c.c. 

Hyposulphite  of  soda   (dried  powder)  %  oz.  15  grams 

Acetic  acid  3  oz.  90  c.c. 

Alum   (powdered)  %  oz.  15  grams 

This  fixing  bath  is  also  recommended  for  plates  and 
films.  It  Avill  keep  indefinitely  and  therefore  may  be  made 
up  some  time  in  advance.  One  pint  of  the  bath  should  fix 
at  least  fifty  4x5  prints.    The  acid  fixing  bath  can  be  used 


510  experime:n^tal  phaemacology 

repeatedly.  It  will  by  degrees  become  alkaline  by  the  grad- 
ual addition  of  developer  adhering  to  the  prints.  It  should 
be  discarded  entirely  when  it  becomes  frothy,  and  a  fresh 
bath  prepared. 

In  fixing,  the  prints  should  be  placed  in  the  bath  face 
doA\aiward.  They  should  be  kept  well  separated  and  in  mo- 
tion for  a  few  seconds  until  the  solution  is  evenly  distributed 
over  them.  From  15  to  20  minutes  should  be  a  sufficient 
length  of  time  to  insure  proper  fixing.  The  prints  should 
then  be  thoroughly  washed  in  water  and  dried.  This  may 
be  done  by  spreading  them  out  face  upward  on  a  large  sheet 
of  paper  in  a  quiet  place  where  dust,  etc.,  cannot  fall  on 
them. 

After  the  prints  are  thoroughly  dried  they  may  be 
trimmed  to  the  desired  size  and  mounted  by  applying  mount- 
ing paste  to  the  back  of  the  print  Avith  a  brush,  after  which 
the  print  is  placed  in  position  on  a  card  mount  and  rolled 
doA^^l  smoothly  with  a  squeegee  roller. 

Blue  Prints. — One  of  the  simplest  of  all  photographic 
processes  is  the  making  of  blue  prints,  which  require  only 
to  be  printed  and  then  washed  thoroughly  in  water.  Blue 
print  paper  is  sensitized  by  the  application  to  the  paper  of 
a  solution  of  ferric  ammoniocitrate  and  ferricyanide  of 
potassium.    The  process  may  be  carried  out  as  follows : 


Solution  A 

Ferric  ammonium  citrate 

lYs 

oz. 

Water 

Solution  B 

8 

oz. 

Potassium  ferricyanide 

1% 

oz. 

Water 

8 

oz. 

To  make  the  sensitizing  bath,  take  equal  parts  of  each 
solution  in  a  tray  or  flat  dish  a  little  larger  than  the  paper 
you  wish  to  sensitize.  Float  the  paper  on  this  bath  for  two 
or  three  minutes,  being  very  careful  to  avoid  any  air  bubbles 
that  may  prevent  the  solution  from  reaching  the  paper. 
Hang  up  the  paper  to  dry.    This  whole  process  of  sensitizing 


MAKING    BLUE    PRINTS  511 

and  drying  (and  preserving)  the  paper  should  be  carried 
out  in  the  dark  room  by  the  ruby  light.  The  paper  should 
not  dry  too  slowly. 

The  two  stock  solutions  will  keep  indefinitely,  but  should 
be  mixed  only  immediately  before  use  as  they  soon  spoil 
after  mixing. 

An^^  fine  grained  white  paper  may  thus  be  sensitized. 
For  all  routine  work  in  the  laboratory,  hoAvever,  it  is  advis- 
able to  buy  ready  prepared  blue-print  paper.  This  should 
be  of  the  finest  quality  as  the  success  or  failure  of  the  whole 
work  depends  on  the  quality  of  the  paper.  It  can  be  bought 
in  rolls  about  30  to  36  inches  in  width  and  of  practically 
any  desired  length  (from  F.  Weber  &  Co.,  Philadelphia, 


Fig.  390. — Frame  for  making  blue  prints.  This  frame  is  18  inches  long  by  8  inches 
wide.  It  is  often  advisable  to  use  considerably  larger  frames  if  many  blue  prints  are  to 
be  made. 

St.  Louis,  and  Baltimore).  It  should  be  thoroughly  pro- 
tected from  the  light  and  should  be  fresh  Avhen  used.  The 
paper  bought  should  be  a  li(/ht  iveight  variety  suitable  for 
printing  in  sunlight. 

The  most  important  use  for  blue-print  paper  in  the  lab- 
oratory is  for  the  making  of  multiple  copies  of  the  kymo- 
graph records  obtained  by  students.  For  this  Avork  a  large 
printing  frame  (several  of  these  should  be  proA-ided)  as 
shoAA'U   in  Fig.  390   is  used.     Tliese  frames   are  about   8 


512  EXPERIMENTAL    PHARMACOLOGY 

inches  wide  by  18  inches  long.  They  are  made  exactly  like 
the  ordinary  photographic  printing  frames  and  a  glass  plate 
is  placed  in  the  front  of  the  frame.  Against  this  plate  the 
varnished  black  tracing  (which  should  have  been  smoked 
thoroughly  black)  is  placed  (facing  outward).  Over  the 
tracing  a  suitable  sized  piece  of  blue  print  paper  is  placed 
(this  is  done  in  the  dark  room)  facing  outward,  i.  e.,  the 
blue  side  of  the  paper  rests  against  the  back  of  the  tracing. 
The  back  is  clamped  into  the  frame  and  the  bright  sunlight 
is  allowed  to  shine  through  the  glass  for  a  period  varying 
from  five  to  fifteen  minutes  depending  on  the  quality  of 
the  blue-print  paper,  the  character  of  the  black  tracing  and 
the  brightness  of  the  sun.  With  a  very  bright  sunlight 
and  first  class  printing  paper  the  exposure  should  not  ex- 
ceed ten  minutes  on  the  average  (and  may  often  not  require 
over  five  minutes).  But  much  blue-print  paper  on  the 
market  is  not  this  sensitive.  Poor  paper  should  be  scru- 
pulously avoided.  Only  experience  can  serve  as  a  very  re- 
liable guide  to  one  in  determining  when  an  exposure  has 
been  carried  far  enough.  The  statement  is  made  that,  for 
ordinary  photographic  negatives,  the  printing  should  be 
carried  on  until  the  shadows,  that  is,  the  darkest  parts  of  the 
picture,  assume  a  bronzed  appearance.  In  printing  kymo- 
graphic  records  the  printing  should  be  carried  on  until  the 
print  looks  considerably  darker  than  one  would  at  first  sus- 
pect to  be  necessary,  for  the  washing  removes  some  of  the 
coloring  material. 

As  soon  as  the  printing  has  gone  far  enough  the  pape" 
is  taken  out  and  washed  thoroughly  in  clear  water.  The 
print  is  then  hung  up  to  dry  after  which  it  can  be  properly 
trimmed  and  pasted  in  the  note  book. 

It  is  strongly  advisable  for  some  one  who  is  employed  by 
the  laboratory  (technician,  etc.)  to  make  up  all  blue-prints 
required  by  the  students.  These  prints  can  be  sold  to  the 
students  for  about  one-half  or  one  cent  apiece  (which  prac- 
tically covers  the  cost  of  the  paper),  and  the  proceeds  of  the 
sale  should  go  to  the  person  who  makes  the  prints.    In  most 


MAKING    BLUE    PKINTS  513 

schools  the  students  will  not  have  sufficient  time  to  make 
up  their  ovni  blue-prints.  Much  time  may  be  saved  in  print- 
ing if  very  large  frames  (two  feet  square  or  larger)  are 
used  since  the  whole  frame  can  be  filled  and  printed  at  one 
time.  The  instructor  should  see  that  blue-prints  are  made 
only  from  typical  and  satisfactory  records,  and  each  print 
should  be  made  as  small  as  possible  to  include  the  required 
portion  of  the  record.  Copies  of  kymographic  records  may 
also  be  printed  on  regular  photographic  printing  paper  and 
developed  and  fixed  in  the  usual  manner.  This  is  more  ex- 
pensive but  is  often  available  for  special  work. 


A  LIST  OF  DEALERS  IN  APPARATUS,  TOOLS,  SUP- 
PLIES, EQUIPMENT,  ETC. 

The  following  list  of  dealers  in  apparatus,  tools,  supplies, 
equipment,  etc.,  is  by  no  means  complete,  but  is  merely  of- 
fered for  the  benefit  of  those  who  may  not  know  the  sources 
from  which  certain  desired  articles  can  be  obtained.  In  all 
large  cities  laborator^^  workers  will  be  familiar  with  local 
firms  from  which  a  considerable  proportion  of  the  usual 
laboratory  supplies,  etc.,  may  be  obtained.  But  special  ar- 
ticles (and  these  are  often  needed)  may  be  difficult  to  se- 
cure. It  is  hoped  that  the  appended  list  may  be  of  some  aid 
in  this  direction. 

Armstrong  Bros.  Tool  Co.,  Chicago,  111. 

(Tool  holders  and  metal  cutting  tools.) 

American  X-Eay  Equipment  Co.,  401-405  East  33rd  St.,  New  York  City,  N.  Y. 
(X-ray  apparatus,  etc.) 

TTie  Anglers  Co.,  913  West  Eandolph  St.,  Chicago,  111. 
(Biological  supplies,  frogs,  etc.) 

Ansco  Company,  Binglianiton,  N.  Y. 
(Photographic  supplies.) 

Armonr  ^-  Company,  Chicago,  111. 
(Pituitary  extract.) 

Bmrd  ^  Tatlock,  Ltd.,  14  Cross  St.,  Hatton  Garden,  London,  E.  C. 
(Physiological  apparatus.) 

Brown  ^  SImrpe  Mfg.  Co.,  Providence,  R.  I. 
(Small  hand  tools  and  machine  supplies.) 

Buffalo  Dental  Mfg.  Co.,  Buffalo,  N.  Y. 

(Laboratory  and  workshop  appliances,  blast  lamps,  etc.) 

Benedict  cj-  Burnham  Mfg.  Co.,  Waterbury,  Conn. 
(Seamless  nickel  tubing.) 

Chas.  E.  Besley  Co.,  118-124  N.  Clinton  St.,  Chicago,  111. 
(Brass,  copper,  gears,  tools,  machine  supplies,  etc.) 

J.  T.  Baker  Chemical  Co.,  Phillipsburg,  N.  J. 
(Chemicals.) 

James  G.  Biddle,  1211-13  Arch  St.,  Philadelphia,  Pa. 
(Electrical  instruments  and  laboratory  supplies.) 

Burroughs,  Wellcome  cj-  Co.,  35-39  West  33rd  St.,  New  York  City,  X.  Y. 
(Drugs  and  physicians'  supplies.) 


516  EXPERIMENTAL    PHARMACOLOGY 

Boston  Gea/r  WorTcs,  Norfolk  Downs,  Mass. 

(Gears,  racks,  clutches,  roller  chains,  etc.) 

Baiisch  ^  Lotrib  Optical  Co.,  Eoehester,  N.  Y. 

(Optical  goods,  balopticons,  lenses,  microscopes,  and  supplies.) 

J.  G.  Blount,  Everett,  Mass. 

(Grinding  and  polishing  machinery,  speed  lathes,  etc.) 

Becton-Dickmson  4'  Co.,  Eutherford,  IST.  J. 
(Clinical  thermometers.) 

Bishop  Gutta-Percha  Co.,  420  East  25th  St.,  New  York  City,  N.  Y. 
(Sheet  gutta-percha.) 

W.  J.  BoeJim,  West  Eandolph  St.,  Chicago,  111. 
(Blows  glass  arterial  cannulas.) 

Burke  #  James,  Inc.,  240  E.  Ontario  St.,  Chicago,  111.,  and  225   Fifth  Ave., 
New  York  City,  N.  Y. 
(Photographic  supplies,  etc.) 

Crane  Co.,  Chicago,  111.,  and  St.  Louis,  Mo. 

(Steam  fittings,  gas  fittings,  and  plumbers'  supplies.) 

S.  W.  Card  Mfg.  Co.,  Mansfield,  Mass. 
(Taps,  dies,  screw  plates,  etc.) 

Croivell  Mfg.  Co.,  296-298  TaafPe  Place,  Brooklyn,  N.  Y. 

(Air  compressors,  vacuum  pumps,  and  pressure  blowers.) 

Central  Scientific  Co.,  345-359  West  Michigan.  St.,  Chicago,  111. 
(Biological  apparatus  and  supplies.) 

Commercial  Electrical  Supply  Co.,  15th  and  Pine  Sts.,  St.  Louis,  Mo. 
(Electrical  supplies.) 

Canedy-Otto  Mfg.  Co.,  Chicago  Heights,  111. 

(Forges,  blowers,  punches,  shears,  drills,  etc.) 

Cooper  Eeivitt  Electric  Co.,  8th  and  Grand  Sts.,  Hoboken,  N.  J. 
(Electric  lamps.) 

Cramer  Dry  Plate  Co.,  Shenandoah  and  Lemp  Aves.,  St.  Louis,  Mo. 
(Photographic  dry  plates.) 

Edward  P.  Dolbey  cf  Co.,  3613  Woodland  Ave.,  Philadelphia,  Pa. 
(Chemicals  and  laboratory  apparatus.) 

Defender  Photo  Supply  Co.,  Argo  Park,  Eoehester,  N.  Y. 
(Photographic  dry!  plates,  paper,  etc.) 

Detroit  Copper  ^  Brass  Boiling  Mills,  Detroit,  Mich. 
(Copper  or  brass  sheeting,  tubing,  rod  and  wire.) 

Detroit  Dental  Mfg.  Co.,  Detroit,  Mich. 

(Impression  compound  and  dental  supplies.) 

Day  Eubber  Co.,  415-417  North  4th  St.,  St.  Louis,  Mo. 
(Eubber  supplies.) 

Louis  Dejonge  ^-  Co.,  P.  O.  Box  553,  New  York  City,  N-  Y. 
(White  coated  paper.) 

Eimer  ^  Amend,  205-211  Third  Ave.,  New  York  City,  N.  Y. 
(Laboratory  apparatus,  chemicals  and  drugs,  importers.) 

Eherhach  4"  Soirk  Co.,  Ann  Arbor,  Mich. 

(Laboratory  supplies,  special  pharmacological  apparatus.) 


DEALERS    IN    SUPPLIES    AND    EQUIPMENT  517 

Fariicerche-Hoechst  Company,  New  York  City,  N.  Y. 
(Special  drugs,  novocaine,  salvarsan,  pyramidon,  etc.) 

Ft.  Wayne  Electric  Co.,  Ft.  Wayne,  Indiana. 
(Motors  and  electrical  supplies.) 

G.  Gennert,  New  York,  Chicago,  Los  Angeles,  and  San  Francisco. 
(Photographic  supplies,  etc.) 

Gregory  Electric  Co.,  16th  and  Lincoln  Sts.,  Chicago,  111. 
(Second  hand  motors  and  electric  supplies  of  all  kinds.) 

Goodyear  Bubber  Co.,  411  North  4th  St.,  St.  Louis,  Mo. 
(Rubber  supplies.) 

Hoffmann-LaBoche  Chemical  Worhs,  New  York  City,  N.  Y. 
(Opium  alkaloids,  pantopon,  etc.) 

Hammer  Dry  Plate  Co.,  Ohio  Ave.  and  Miami  St.,  St.  Louis,  Mo. 
(Photographic  dry  plates.) 

Hettinger  Bros.  Mfg.   Co.,  Kansas   City,   St.  Louis,   Mo.,   or   Oklahoma   City, 
Oklahoma. 
(Dental  wax  and  dental  supplies.) 

Harvard  Apparatus  Co.,  Back  Bay  Post  OiBce,  Boston,  Mass.    v 
(Physiological  laboratory  apparatus.) 

Henry  Heil  Chemical  Co.,  210-214  S.  Fourth  St.,  St.  Louis,  Mo. 
(Laboratory  apparatus,  chemicals  and  supplies,  importers.) 

F.  A.  Hardy  ^-  Co.,  Chicago,  111. 
(Optical  goods.) 

International  Equipment  Co.,  352  Western  Ave.   (Brighton),  Boston,  Mass. 
(Centrifuges  and  mechanical  apparatus.) 

Kny-Scheerer  Co.,  404-410  West  27th  St.,  New  York  City,  N.  Y. 
(General  laboratory  supplies,   chemicals,   importers.) 

C.  A.  F.  Kahlhaum,  Berlin,  Germany. 
(Chemicals.) 

L.  E.  Knott  Apparatus  Co.,  Boston,  Mass. 
(Biological  apparatus  and  supplies.) 

Kimble-Durand  Glass  Co.,  Chicago,  111.,  New  York  City,  and  Yineland,  N.  J. 
(Laboratory  glassware,  glass  blowing,  cannulas,  etc.) 

Kewaunee  Mfg.  Co.,  Kewaunee,  Wis. 

(Laboratory  furniture  and  equipments.) 

The  Libbey  Glass  Co.,  Toledo,  Ohio. 
(Chemical  glassware.) 

Lennox  Chemical  Co.,  1201-1215  East  55th  St.,  Cleveland,  Ohio. 
(Oxygen,  nitrous  oxide  and  carbon  dioxide.) 

E.  Leitz  4-  Co.,  30  East  18th  St.,  New  York  City,  N.  Y. 
(Microscopes,  optical  goods,  etc.) 

Lens  Apparatus  Co.,  Inc.,  9-11  East  16th  St.,  New  York. 

(Chemicals,   drugs,   stains;    chemical,  medical,   surgical   and   physical   ap- 
paratus; glassware.) 

Eli  Lilly  di'-  Co.,  Indianapolis,  Ind. 

(Biological  and  pharmaceutical  i^roduets.) 


518  EXPERIMEI^TAL    PHARMACOLOGY 

John  T.  Milliken  cf-  Co.,  St.  Louis,  Mo. 
(Pharmaceutical  supplies.) 

H.  E.  Mulford  Co.,  Philadelphia,  Pa. 

(Biological  and  pharmaceutical  supplies.) 

George  Murphy,  Inc.,  57  East  9th  St.,  New  York  City,  N.  Y. 
(Photographic  supplies,  lantern  slide  labeling  strips,  etc.) 

Mcintosh  Stereopticon  Co.,  460  Atlas  Block,  Chicago,  111. 

(Stereopticons  and  ox^tical  supplies,  lantern  slides,  etc.) 

F.  Mueller  4'  Co.,  1779  Ogden  Ave.,  Chicago,  111. 
(General  surgical  supplies.) 

Murray  Oxygen  Co,,  449  West  53rd  St.,  New  York  City,  N.  Y.;  309  South  5th 
St.,  Philadelphia,  Pa.;  102  Utica  St.,  Boston,  Mass. 
(Oxygen  and  nitrous  oxide.) 

£■.  Machlett  #  Son,  153  East  84th  St.,  New  Y^ork  City,  N.  Y. 
(All  kinds  of  glass  blowing.) 

Morse  Tivist  Drill  4-  Machine  Co.,  New  Bedford,  Mass. 

(Twdst  drills,  chucks,  cutters,  dies,  taps,  and  machinists'  tools.) 

MalUncTcrodt  Chemical  Worlcs,  2nd  and  Mallinckrodt  Sts.,  St.  Louis,  Mo. 

(Chemicals    for    medicinal,    photographic,    analytical    and    technical    pur- 
poses, ether  for  anesthesia,  etc.) 

MercH  4^  Co.,  4528  S.  Broadway,  St.  Louis,  Mo.,  and  Rahway,  N.  J. 
(Drugs  and  chemicals.) 

The  Miller  Buiier  Co.,  Akron,  Ohio. 
(Finger  cots.) 

Norton  Company,  Worcester,  Mass. 

(Alunduni  and  crystolon  grinding  wheels.) 

E.  B.  Neuenfelclt  4-  Co.,  225  North  Clark  St.,  Chicago,  111.   ^ 
(Turtles,  frogs,  etc.) 

C.  F.  Palmer,  6  Upper  Tulse  Hill,  Brixton,  London,  S.  W. 
(Brodie's  physiological  apparatus,  etc.) 

Palo  Company,  90-94  Maiden  Lane,  New  York  City,  N.  Y. 
(Laboratory  supplies  and  assayers'  materials.) 

Pilce  Mfg.  Co.,  Pike,  N.  H. 
(India  oil  stones.) 

Pennsylvania  Flexible  Metallic  Tubing  Co.,  People's  Gas  Bldg.,  Chicago,  111. 
(Flexible  metal  tubing.) 

Poivers-Weightman-Bosengarten  Co.,  Philadelphia,  Pa. ;  New  York  City,  N.  Y., 
and  St.  Louis,  Mo. 
(Chemicals  and  drugs.) 

Prtrfce,  Davis  4'  Co.,  Detroit,  Mich.     (Branch  houses  in  other  cities.) 
(Drugs,  extracts,  tinctures,  etc.) 

The  Bobbins  4'  Myers  Co.,  Springfield,  Ohio. 
(Motors  and  electrical  supplies.) 

A.  A.  Spimng,  North  Judson,  Indiana. 
{Turtles,  frogs,  etc.) 

Southern  Oxygen  Co.,  South  Washington,  Virginia. 

(Oxygen  and  hydrogen.)  , 


DEALERS    IjST    SUPPLIES    AND    EQUIPMENT  519 

J.  T.  Slocomh  Co.,  Providence,  R.  I. 
(Machinists'  tools.) 

,St'«ra,  Hochucl-  <f-  Co.,  Chicago,  III. 
(Supplies  in  general.) 

Sharp  4'  Smith,  92  Wabash  Ave.,  Chicago,  111. 
(Hospital  supplies,  surgical  instruments,  etc.) 

E.  B.  Sqiiibb  4'  Sons,  Manufacturing   Chemists,  New  York  City  and  Brook- 
lyn, N.  Y. 
(Ether  and  chemicals.) 

Stanley  Bule  4"  Level  Co.,  New  Britain,  Conn. 
(Small  hand  tools.) 

Spencer  Lens  Co.,  Buffalo,  N.  Y. 

(Microscopes,  lenses,  and  optical  goods.) 

The  Silver  Mfg.  Co.,  Salem,  Ohio. 

(Woodworking  and  blacksmiths'  tools.) 

E.  E.  Sargent  ^  Co.,  143-145  Lake  St.,  Chicago,  111. 

(Scientific  laboratory  apparatus,  chemicals,  rubber  tubing,  etc.) 

Standard  Scientific  Co.,  147-153  Waverly  Place,  New  York  City,  N.  Y.  J 
(Standard  apparatus  and  chemicals.) 

Scientific  Materials  Co.,  713-719  Forbes  St.,  Pittsburgh,  Pa. 
(Laboratory  supplies  and  chemicals.) 

Seneca  Falls  Mfg.  Co.,  Seneca  Falls,  N.  Y. 
(Lathes  and  attachments.) 

Talbot  Dyewood  4'  Chemical  Co.,  Billerica,  Mass. 
(Acids  and  chemicals.) 

Thau  4"  Nolde,  Frisco  Bldg.,  St.  Louis,  Mo. 
(Dental  rubber  dam  and  dental  supplies.) 

Arthur  H.  Thomas  Company,  West  Washington  Square,  Philadelphia,  Pa. 
(Laboratory  apparatus  and   chemicals,  importers.) 

Truax,  Greene  4"  Co.,  42-44-46  Wabash  Ave.,  Chicago,  111. 

(Laboratory  apparatus,  chemicals,  surgical  supplies,  etc.) 

Victor  Animatograph  Co.,  Inc.,  Davenport,  Iowa. 

(Portable  stereopticons,  sundries,  lantern  slides,  etc.) 

Victor"  Electric  Corporation,  Jackson  and  Robey  Sts.,  Chicago,  111. 
"(Laboratory  electric  equipments,  X-ray  machines,  etc.) 

F.  Weber  4"  Co.,  Philadelphia,  St.  Louis,  and  Baltimore. 

(Draughtsmen's   and    engineers'    supplies,    artists'   materials,   blue    print 
paper.) 

Wilmot  Castle  Co.,  Rochester,  N.  Y. 
(Bacteriological  apparatus,  etc.) 


GENERAL   INDEX 


Abdominal    viscera,    dog,    dissection 

to  show,  167 
Absorption,  of  ether,  124 

through  skin  in  frog,  118 
Acetanilide,  action  on  fever,  451 
Acetylsalicylic  acid,  action  on  fever, 

451 
Acid,  acetylsalicylic,  451 

action   in  migraine,  451 
and  alkali,  466 

carbolic,  antidote  for,  454,  456 
general  action  on  dog,  454 
general  action  on  frog,  454 
hydrocyanic,  441 
soldering,   483 
Acids,   action    of,    on    frog's    blood- 
vessels, 458 
Aconitine,  392 

action   on   blood-pressure,   respira- 
tion,   and    temperature,   429 
on  frog's   heart,  429 
on     heart     and     blood-f»ressure, 

431,  432 
on  turtle's  heart,  429 
general  action  of,  on  frog,  428 
local  action,  433 
Adjustable  tambour,  40,  483 
Administration    of    tablets    to    dog, 

205 
Adrenal    glands,    action    of    pilocar- 
pine on,  278 
Adrenaline,    action    on    bladder    and 
intestine,  278,  280,  281,  282 
on  blood-j^ressure  after  ergotox- 

ine,  378 
on  bronchioles,  387 
on    bronchioles,    after    ergotox- 

ine,  378,  379 
on  dog's  heart,  156 
on  frog's  blood-vessels,  458 
on   intestinal   segment,   334 
on  liver,  417 
on  lymph  flow,  384 
on  perfused  kidney,  342 
on      pulmonarv     blood-pressure, 
310-318,  369,  372 
action    rate    of    oxygen    consump- 
tion, 192 
glycosuria,  457 


Adrenaline — Cont  'd. 

in   reviving  heart,   113 
synthetic,  96 
Agurine,   253 
Air   embolism,   226 
Air  pumps,  473,  474,  475,  476,  477 
Alcohol,  action  on  blood-pressure  and 
respiration,  136,  142 
on  frog,  133 
on  turtle's  heart,  135 
antiseptic   action   of,   157' 
ethyl,    methyl,    amyl,    136 
Alkali  and  acid,  466 
Alkali  to  absorb  C0„,  119 
Alkalis,    action   on   chloral   hydrate, 
172 
action  on  frog's  blood-vessels,  458 
Aluminum  soldering^  489 
Ammonia,  462 

Amylnitrite,    action    of,    on    corpus- 
cles in  retina,  400 
on  retinal   vessels,  401 
on  sphygmograph,  399,  400 
on  vision,  403 
general  action  of,  404 
]3lethysmograph    and    general    ae- 
^  tion,   397,   398 
Analgesia,    nitrous    oxide,    120 
Anatomy  of,  cat's  heart,  426 
dog's  heart,  427 
eye,  394 

frog's  brain,  55 
frog's  heart,  69 
Anesthesia,   by    ethyl    chloride,    127 
by  intratracheal   insuflPlation,    129 
closed  method  of,  121,  122,  127 
local,   351 
nitrous  oxide,  119 
spinal,  356 
Anesthetization   of   dog,    77 
Aneurism  needles,  49 
Animal   operating  boards,   43 
Animals,  disposal  of  dead,  102 
Annulus   Vieussenii,   143,   155 
Ansa  subclavia,  143,  155 
Anticoagulating  solutions,  96 
Antimony    (tartar   emetic),   462 
Antipyrine,     action     on     blood-pres- 
sure,    respiration     and     leg 
volume,  449 


522 


GENERAL    INDEX 


Antipyrine — Cont  'd. 
action  on  fever,  451 
frog,   general  action,  449 
Antiseptic  action  of  aleoliol,  lai" 
Anvils,   485 

Apomorphme,   emesis,  440 
Apparatus,  arranged  for  several  rec- 
ords on   drum,   165 
for    administering    nitrous    oxide, 

130 
for  intratracheal  insufflation,  129 
for  perfusion  of  excised  heart,  425 
for   recording,   cerebrospinal   fluid 
pressure,   159 
esoptiageal  contractions,   137 
fatigue  tracings,  245 
pulmonary    blood-jpressure,    311 
rate     of     oxygen     consumption, 

180-183 
reaction  time,  143,  146 
individual,  48 
permanent,  list  of,  34 
Arc  light,  adjustable,  500,  501 
Arecoline,  action  of,  on  bladder  and 
intestine,  278,   298 
on  blood-pressure,  278,  282,  298 
on  bronchioles,  278,  298 
on  frog's  retinal  circulation,  274 
on  heart,  299 

on  intrathoracic  pressure,  282 
on    pupil,    275 
on  respiration,  298 
Armstrong,  boring  out   tool,  488 
cut  off  tool,  488 
threading  tool,  488 
Arrangement  of  operating  table,  123 
Arsenic,  general  action,  460 
Arterial  cannula,  42 
Arterial  cannulas,  brass,  method  for 

making,  496 
Artery,  carotid,  dissection  for,  90 
femoral,   107 
mammary,  194 

pulmonary,   112,   306,   313,   314 
subclavian,    142 
vertebral,  193,   195 
Artificial  respiration,   108,   111 
Artificial  respiration  faucet.  111 
Artificial  respiration  machines,  473- 

477 
Asphyxia,  death  by,  128 
Aspirin,  action  on  fever,  451 

action  on  headache,  451 
Assay  of  digitalis,  414 
Assay  of  ergot,  rooster's  comb,  361 
Assignment  of  tables,  33 
Atmospheric  pressure,  increased  ac- 
tion of,  117,  118 


Atmospheric  pressure — Cont  'd. 

reduced  action  of,  119 
Atropine,     action     of,     on     bladder 
and  intestine,  278,  280 
on     blood-pressure,     respiration 

and  heart,  270,  275 
on  bronchioles,  287,  295 
on   intrathoracic   pressure   after 

arecoline,  282 
on  chorda  tympani  nerve,  270 
on     frog's     heart     and     vagus. 

nerves,  268,  273 
on  frog's  muscle  and  nerve,  269 
on  frog's  pupil,  269,  275 
on  frog's  retinal  circulation,  274 
on   intestinal   segment,   334 
on  pancreatic  secretion,  270,  275' 
on  pupil,  269 

on  ring  of  frog's   stomach,  337 
on  salivary  secretion,  270,  275 
on   sweat   secretion,   270 
adrenaline,    action    of    on    blood- 
pressure,      respiration      and 
bladder,    346 
Attaching      animal      to      operating- 
board,  method  of,  83 

B 

/3-iminazololylethylaniine      (see     Er- 

gamine) 
/3-tetrahydronaphthylamine       hydro- 
chloride, 449,  450,  453 
Bandage  saw,  hand,  108 
BarlDour  's  method  for  recording  uter- 
ine contractions,  363,  364 
Barium,  363,  365 

action   of,   on  bladder,   278 

on    blood-pressure    and    respira- 
tion,  278 
on  bronchioles,  287 
on  intestinal  contractions,  353 
on  intestine,  278,  280 
on   intraocular  pressure,  353 
on  heart,  285,  286 
on  perfused  kidney,  342 
on     pulmonary     blood-pressure, 
310-318 
Bath,  fixing,  for  plates,  504 
Battery  jar,  47 

Bayliss-Starling  intestinal  reflex,  468 
Beaker,  43 

Becht's       method       for       recording 
changes      in      cerebrospinal 
fluid,  159 
Bell-jar  for  anesthetizing  cats,  148 
Bellows,  foot,  472 
hand,  107 


GENERAL    INDEX 


523 


Bench,  work,  485 

Bending  glass  tubes,  494 

Benedict's  test   for  glucose,   17G 

Bernard 's   experiment,   255 

Bert 's   experiment,   120 

Binding  strips  for  lantern  slides,  508 

Binz  's    experiment,   447 

Biological   supplies,    dealers    in,   list 

of,   515 
Bits,  485 

Bladder,  action  of,  adrenaline, 
atropine,  arecoline,  barium 
on,  278 
lobeline,  adrenaline,  pilocarpine 
and  tetramethylammonium 
chloride,  325 
cannula,  44 

method  of  inserting,   188 
contractions,  346 
recording,  206 
recording  apparatus  for,  207 
innervation  of,  384 
Blast  lamp,  482,  483 
Blood,   action  of,  cyanides   on,  441 

nitrites  on,  404 
Blood-pressure,     action     of,     chloro- 
form on,   77 
digitoxin  on,  408-413 
ether  on,   77 
ethyl  bromide  on,  77 
ethyl  chloride  on,  127 
nitrous  oxide  on,  126 
somnoform  on,   127 
tetramethylammonium     chloride 
on,       before       and       after 
atropine,  329 
compensation  of,  196 
in  spinal  dog,  211 
recording,  method  of,  96 
Blowing  of  glass,  492-495 
Blow  pipe,  489 
Blue  print  paper,  510,  511 
Blue  prints,   51 

method  for  making,  510-513 
Boards,  operating,  43 

frog,  54 
Bone  cutting  forceps,  326 
Bottle,  pressure,  37,  97 
Box   for   anesthetizing   cats,   147 
Brace  and  bits,  485 
Brachial  plexus,  dog,   142 
Brain  of  cat,  dorsal  view,  180 
of  dog,  base,  17 

motor   areas,   106 
of  frog,  54,  55 
Brandy,  136 
Brass  castings,  497 
Brass  lacquering,  498 


Brass,  supplies  of,  480 

Brazing,   492 

Bronchial  changes,  independent  of 
pulmonary  pressure,  198 

Bronchiole  changes,  method  of  re- 
cording, 196,  206,  210.  227, 
228,  278,  288,  290,  291,  298 

Bronchiole  tracings,  special  appara- 
tus for  obtaining,  288-290 

Bronchioles,  action  of,  ergamine  on, 
373,  376 
opium  alkaloids  on,  194 
nitrites  on,  406 

Brucine,   action   of,   on  frog,   233 

Brugg's  mixture,  127 

Bulb,  mercury,  206 

Burnishing,  487 

C 

Caft'eine,    action    of,    on    blood-pres- 
sure and  respiration,  249 
on  frogs,  241 

on  heart  and  vagus  nerve,  244 
on  muscles,  243 
on  nerves,  243 
diuresis,  247,  249 
effect  on   reaction  time,   244 
Calcium,  antagonizes  magnesium  an- 
esthesia,  460 
Calipers,  487 
Cameras,  500 
!    Canals,  semicircular,  in  i^igeon,  174 
■   Cannabis  indica,  action  on  dog,  205 
'    Cannula,  arterial,  glass,  42 
I        bladder,   44 

carotid,   method   of   inserting,   85 
insertion  of,  in  pancreatic  duct,  268 
1        insertion      of.      into      Wharton's 
\  duct,   266 

I        straight,  glass,   107 

tracheal,   method   of   inserting,   85 

method  of  making,  490 
ureteral,  225 
with   special  points,  247 
with  special  washout.  248 
!    Cannulas,  brass,  method  for  making, 
496 
glass,  blowing,  492,  495 
special  for  pulmonary  artery,  315 
tracheal,  39 
Capillarv  circulation,  action  of  ergot 
'  on,  361,  362 
method  of  observing,  362 
Carbolic   acid,  454.  456 
Carbon  dioxide,  action  on  blood-pres- 
I  sure  and  respiration.  131 

I  on  frog,  113 


524 


ge:n"eral  index 


■Carbon-dioxide — Cont  'd. 
generator,   Guthrie's,   116 
tank  yokes,  115,  116 
Cardiac  nerve,  inferior,  142 

superior,  142,  257 
Cardiac  sympathetic  nerves,  155 
Cardiographic     tracing,     action     of 

adrenaline   on,   156 
Cardiographic    tracings,    method    of 

recording,  152 
Cardiometer,    107,   110,   112 
thistle  tube,  151 
used  as  a  myocardiograph,  150 
Carotid   artery,   274 
dissection  for,  90 
dog.  142 
rabbit,   247 
Casserole,  44 

Castings,  for   stands,   etc.,  496 
Cat,  dose  of  paraldehyde  for,  254 
dose  of  urethane  for,  254 
lymphatic  system  of,  386 
Catheter   for   intratracheal   insuffla- 
tion,   132 
Catheters,  216 

Cat's   brain,    dorsal   view    of,    180 
Cat's   heart,   426 
Cat's  skull,  mesial  section  of,  179 

upper  surface  of,  178 
Cause  of  death  under  coniine,  268 
Center,  crotch,  488 

vasoconstrictor,      action      of,      in 

shock,  166 
vomiting,   440 
Cerebrospinal   fluid,    action   of   alco- 
hol on,  158 
Cerebrum,  anatomy  of,  in  frog,  54,  55 
cutting  off,  in  frog,  238 
removal  of,  in  frog,  54 
Cervical  ganglion,  inferior,  142 

superior,  274,  394 
Cervical     sympathetic     nerve,     142, 

194,  247 
Cervical    sympathetic,    dog,    77,    274 
Cervical  vagi,  dog,  77 
Chamber,  gas,  58 

Chemical  supply  houses,  list  of,  515 
Chest,   opening,   102 
Chest  oncometers,   288,   289 
Cheyne-Stokes  respiration,  176,  190, 

355 
Chloral  hydrate,  229 

action  of,   alkalis   on,   172 
on  frog,  168 
on  frog's  heart,  169 
on   retinal    circulation,    169 
on  turtle's  heart,  172 


Chloretone,  354 

action  of,  on  frog,  168 
Chloroform,     action     of,     on     blood- 
pressure     and     respiration, 
77,   120 
on  conductivity  and  irritability 

of  nerve,  57 
on  dog  or  cat,  121 
on  frog,  55 
on  frog's  heart,   70 
on    frog's   lymph  hearts,    70 
on  turtle's  heart,   76 
injection  into  artery,  128 
injection  into   carotid   artery,   210 
injection  into  vertebral  artery,  195 
Chorda  tympani,  stimulation  of,  266 
Chorda  tympani  nerve,  257,  259,  266 

action  of  atropine  on,  270 
Chordo-lingual  triangle,  257 
Chronograph,  Jaquet,  82 

Lieb-Becker,    80 
Chuck,  Jacob's  drill,  488 
Chuck's  for  lathes,   488 
Clamp,  bull-do'g,  48 
burette,  46 
double,  46 
Clips,  frog,  method  for  making,  495 
Clock,  time,  80-82 
Closed  anesthesia,  121,  122 
Cocaine,    action    of,    on    blood-pres- 
sure,    respiration     and     in- 
testine, 353 
on  frog,  350 

on  frog's  heart,  351,  352 
on     intraocular     pressure,     and 

local  vascular  action,  353 
on  muscular  work,   352 
on  pupil,  350 
local  anesthetic  action,  351 
Cocks,  Mohr  pinch,  40 
Codeine,   action   on  bronchioles,   194 
on  bronchioles  and  bladder,  106, 

213,  214 
on  frog,  173 

on  oxygen  consumption,   190 
on  turtle  lung,   215 
Compressor,  for  air,  473,  475,  489 
Coniine,    action    of,    on    blood-pres- 
sure and  respiration,   265 
on     froig's     heart     and     vagus 

nerve,  260 
on   intestinal   loop,    265 
on  kidney,  265 
on   salivary  nerves,   265 
on  spleen,  265 

on     turtle 's     heart     and    vagus 
nerve,   260 


GEI^EEAL    INDEX 


525 


Convulsions,   brncino,    233 
recording-  in  a  frog',  218 
strychnine,   224 
Copper,  soldering,  489 
Copper  wire,  484 
Copying,  500,  501 
Counter  sinks,  485 
Crotch  center,  488 
Croton  oil,  466 
Crowell  air  pumps,  473,  489 
Curara,  action  of,  on  blood-pressure 
and  respiration,  257 
on  central  nervous   system,   256 
on   frog,    255 
on  frog's  heart,  256,  257 
on  salivary  nerves,  257 
effect  of,  on  strychnine  action,  257 
Cushny's  method  for  recording  res- 
piration, 99 
Cushny's    myocardiograph,    151 
Cutter,  pipe,   487 
Cyanides,    general    action,   441 
Cycloplegiacs,  273 
Cylinder,  graduated,  44 

D 

Dealers   in   supplies   and   equipment, 

list  of,  515 
Delirium  cordis,  287 
Dental  rubber   dam,   attachment   of, 

to  stethograph,  484 
Depressor  nerve  in  rabbit,  247 
Developers,   502,   503,   504,   508,   509 
Developing,   503 
Develojjing  prints,   509 
Diagram  of  the  involuntary  nervous 

system,  384 
Diaphragm,   dissection  for,   110,   166 
Dies,  485 

Digastric  muscle,  267 
Digitoxin,   action   of,   on  blood-pres- 
sure and  respiration,  408 
on   diuresis,   spleen   volume,   leg 

volume,  420 
on  heart   (dog),  418 
on  heart  (frog  or  turtle),  408 
on  perfused  heart,   424,   425 
on  pulmonary  blood-pressure,  415 
general  action  of,  on  frog,  407 
Dionine,    action    of,    on   bronchioles, 

194,  202 
Dish,  evaporating,  43 
Dissecting  forceps,  49 
Dissecting  probe,  49 
Dissecting  scissors,  49 
Dissection,  for  intraocular  nerves,  319 
for  salivarv  glands  and  duets, 
267,  "274 


Dissection — Cont  'd. 

for  vagus  nerve,  in  frog,  65 

of    brain  and  semicircular  canals, 

pigeon,  174 
of  eye,  394 
of  vagus  and   sympathetic  nerves- 

in  turtle,  75 
to  show  left  kidney,  164 
to  show  lymphatic  ducts,  356,  384 
to  show  pelvic  organs  in  dog,  21(> 
to  show  pulmonary  artery,  312 
Diuresis,  catfeine,  247 
Diuretine,  253 

Do'g,  action  of,  alcohol  on,  136 
cannabis  indiea  on,  205 
carbon  dioxide  on,   131 
chloroform    on,    77 
dose  of  chloretone  for,  233 
ether  on,  77 
ethyl  bromide  on,  77 
heart  levers  for,  154 
spinal,  206 
Dog  boards,  43 
Dog's  brain,  base  of,   175 

motor   areas   of,   106 
Dog's  heart,  427 
Double     pole     double     throw     knife 

switch,  35 
Dreser's  method  for   measuring   ex- 
pired air,  187 
Drill  chuck,  Jacob's,  488 
Drill,  hand,  479,  481 
Drill  press,  488 
Drills,  479,  488 

Drum,  Harvard  long  paper,  45 
Hiirthle,  45 

records,  varnish  for,  62 
stethograph,  41 
Drum   spinning   attachment,   436 
Drums,  smoking,  61 
Duct,  Bartholin's,  257,  267,  274 
Stenson's,   257 
thoracic,      collection      of      lymph 

from  356,  384 
thoracic,  dissection  for,  144 
thoracic,  in  a  cat.  386 
Wharton's,   257,   267.   274 
Ducts,  Ivmphatic,  thoracic,  356,  384^ 
"386 
pancreatic,  226,  252.  268,  278 
Dudgeon 's   sphygmograph,   399 

E 

Ear,  rabbits,  vessels  in  shock,  16(5 
Edmund's  liver  oncometer,  417 
Electric  tuning  fork,  145 
Electric   wiring  system,  471 
Electrodes,  shielded,  Harvard,  38 


526 


GENERAL    INDEX 


Embolism,   air,  226 
Emery  wheel,  487,  495 
Emesis,  440 
Emodin,  468 
Epinine,  124 

Equipment  and  supplies,  list  of  deal- 
ers in,  515 
Equipment  of  shop,  470 
Equipment,  list  of,  for  shop,  479 
Ergamine,  363 

action  of,  on  bronchioles,  373,  378 

on  lymph  flow,  384 
"    on  oxygen  consumption,  268 
on     pulmonary     blood-pressure, 

369,   372 
on  respiration,  367 
on  turtle   lung-^  363 
on  uterine  strip,  380,  381 
OIL  uterus  in  situ,  382 
Ergot,  action  of,  on  capillary  circu- 
lation in  frog,  361 
on  rooster's  comb,  360 
on  uterus  of  cat,  381 
Ergotoxine,   363 

action    on   uterine    strip,   380,   381 
effect  of,  on  bronchioles,  377,  378 
Erigens  nerve,  282 
Eserine,   342 

Esophageal  contractions,  136,  137 
Ether,   action   of,   on   blood-pressure 
and   respiration,    125 
on  conductivity  and  irritability 

on  nerve,   57 
on  dog  or  cat,  121 
on  frog,   53 
on  frog's  heart,  65 
bottle,   milk   bottle,   59 
bottle,  with   by-pass,    111,    126 
bottle,  Woulff,   38 
Etherization   of   dog,  method   of,   77 

of  frog,   53 
Ethyl  bromide,  action  on  dog,  110 

on  dog  or  cat,  121 
Ethyl   chloride,   action  of,   on  blood- 
pressure      and      respiration, 
127 
on  dog  or  cat,  121 
administration,    121 
and  bromide,  action  on  conductiv- 
ity     and      irritability       of 
nerve,  57 
containers,    60 
local   anesthesia,   64 
Experiment,   Paul  Bert's   120 
Expired    air,    Dreser's    method    for 

measuring,  187 
Exposures  photographic,  502 


External  jugular  vein,  142,  194 
Extra  drums  for  records,  101 
Eye,  dissection  of,  394 
innervation   of,   394 
pharmacology     and     anatomy     of, 

394 
symptoms,   certain    ones   following 
adrenaline  and  cocaine,  354 
Eyes,  excision  of,  260 


Fatigue  of  vagus  endings,  133 
Fatigue   tracings,   apparatus   for   re- 
cording,  245 
Fehling's  test  for  glucose,  176 
Femoral  artery,   107 
Fermentation    tube,    157 
Ferric  chloride,  452 
Fever,  451 

Fibrillation  of  heart,  287 
Files,  479 

First  thoracic  ganglion,  142 
Fish  tail  burner,  485 
Fittings,  gas  pipe,  485,  486,  487 
Fixing  plates  or  slides,  504 
Fluid,  cerebrospinal,  action  of  alco- 
hol on,   158 
recording  changes  in,  158,  159 
Foot  bellows,  472 
Foot    of   a   dog,   sweat    secretion   in, 

271 
Forceps,  blunt  pointed,  49,  50 
bone  cutting,  320 
small   sharp   pointed,   48 
Fork,  tuning,   electric,   145 
Former,  for  wood,  488 
Frames  for  blue  printing,   511 
Frog,  action  of,  alcohol  on,  133 
caffeine  on,  241 
carbon  dioxide  on,   113 
cocaine  on,   350 
curara  on,   255 
morphine  on,  172 
nicotine  on,  300 
nitrous  oxide  on,  113 
oxygen   on,   113 
capillary  circulation  in,  362,  363 
destruction  of  cerebrum  in,  238 
exposure  of  brain,  54 
gastrocnemius  muscle,   54 
injection  into  anterior  lymph  sac, 

134 
method  of  exposing  the  heart  of, 

65 
method  of  pithing,  56 
retinal  circulation,   171 
sciatic  nerve,  54 
vagus  nerve,  65 
Frog  board,  54 


GENERAL    INDEX 


527 


Frog  f'li])s,   method  for  making,  495 
Frog    heart,    action    of,    cocaine    on, 

;3r)i 

curara  on,   256 
nicotine  on,  300,  301 
method   of   applying   drugs    to,    68 
Frog    heart    and    nerves,    action    of 

lobeline    on,   322 
Frog  heart  lever,  66 
Frog's    blood-vessels,    perfusion    of, 

458,  459 
Frog's   stomach,   ring   of,   336 

G 

Gag,  mouth,   235 
Ganglia,   spinal,  349 
Ganglion,  first  thoracic,  142 
inferior  cervical,  142 
Meckel's    (spheno-palatine),   265 
superior  cervical,   265,   274 
Ganglionic     paralysis     by     lobeline, 

322,  323,  326 
Gas   reservoir,    186 
Gauge  drill,  487 
pressure,  474 
screw  thread,  487 
wire,   487 
Gebauer's    ethyl   chloride    container, 

60 
Generating  oxygen,  method  for,  185 
Gland,  thyroid,   142 
Glands,    lachrymal,    innervation    of, 
265 
salivary,  innervation  of,  257,  266, 
274 
Glass  blowing,  492-495 
Glucose,    action    of   yeast   and   alco- 
hol on,  157 
in  urine,  176 
Glycogen    stores,    action    of    strych- 
nine on,  224 
Glycosuria,    from    adrenaline,    457 
from  cyanides,  441 
from  phloridzin,  457 
Green 's    method    of    irrigating    the 

heart,   221 
Grouping  of  students,  33 
Guinea  x>ig,  uterine  strip  of,  332,  333 
Gutherie   carbon    dioxide    generator, 
116 

H 

Hack   saw,  479,  488 
Hale's  signal  magnet,  36 
Hammers,   479,   487 
Hand  bellows,  107 
Hand  bracket  saw,  485 
Hand  drill,  479,  481 


Hand    emery    wheel,    487 
Hand  saw,  479 
Handy  valve,  474 
Hatchet,  479 

Harvard,  gas  chamber,  58 
inductorium,   35 
membrane  manometer,   139 
moist  chamber,  57 
muscle  lever,  58 
signal  magnet,  36 
simple  key,  35 
time  clock,  81 
Heart,   action   of,   arecoline   and   at- 
ropine on,  299 
atropine  on,  271 
barium  on,  285,  286 
cocaine  on,  351,  352 
digitoxin  on,  408,  418 
ether  on,  in  frog,  65 
affected    by    high    blood-pressure, 

211 
and  vagus  nerves,  action  of  nico- 
tine on,  in  frog,  300,  301 
action  of  nicotine  on,  in  turtle, 
301 
cat's,  426 
dog's,  427 

effect   of  respiration   of,   110 
frog,  action  of  alcohol  on,  133 
frog,  anatomy  of,  69 
method  of  irrigating,  221 
nerves  to,  in  a  dog,  142,  154 
revival  of,  113 
slowing  by  picrotoxine,  236 
turtle,  exposure  of,  73 
turtle's,   74 
Heart  beat,   reflected   on   lung   trac- 
ings,  216 
Heart  lever  for  frog,  66 
Heart  levers,  for  dogs,   154 
Hearts,  action  of  chloroform  on,   70 

lymph,  frog,   70 
Heart  tracings,  method  of  recording, 

in  a  dog,  152 
Heater,  electric,  487 
Heavy  end  cutting  pliers,  485 
Hemostat,   48 
Heroine,  346,  348 

action  after  lobeline,  326 
action  of,  on  bronchioles  and  blad- 
der, 206,  212 
Hirudin,  to  prevent  coagulation,  197 
Hordenine,  action  of,  on  bronchioles, 

373,   376,  377 
Hydrastinine,     action     of,     on     bron- 
chioles, 242 
Hydrastine,  action  of,  on  frog,  238 
on   frog 's  heart,   240 
on    nerves    of  frog's   heart,   240 
on  nerves  of  turtle's  heart,  241 


528 


GEIiTERAL   INDEX 


Hydrastine — Cont  'd. 

convulsions,  record   of,   239 
Hydrochinon,  metol,  develoiaer,  504 
Hydrocyanic     acid,     general     action, 

441 
Hydrogen  peroxide,  441 
Hydrophobia,  danger  of,   78 

prophylaxis  against,  78 
Hyoscine,  342 
Hyoscyaniine,  342 


Incision  for  femoral  artery,  method 

of,  208 
Incision  for  femoral  vein,  method  of, 

208 
Independence   of   bronchial   changes, 

198 
Inductorium,  Du  Bois-Eej'mond,  36 
Harvard,   35 
holder,   64 
Inferior   cervical   ganglion,   dog,   142 
Inferior  (recurrent)  laryngeal  nerve, 

142 
Inhibition  of  frog's  heart,   133,   134 
Injecting   burette,    93 

method  of  connecting  vein,  93 
Injecting   pipette,   glass,   135 
Innervation  of,  frog's  heart,  240 
heart,  142,  154 
intestine   (small),  336,  384 
pancreas,  268 

retractor  penis  muscle,  282 
salivary  glands,  257 
vessels  in  rabbit's  ear,  166 
Insertion  of  bladder  cannula,   188 
Insertion  of  cannula,  carotid,  85,  91 
femoral  vein,  93,  95 
tracheal,   85 
Insertion  of  cannula  into  pancreatic 

duct,  278 
Insertion  of  lung  shield,  208 
Internal  jugular  vein,   194 
Intestinal     contractions,   action     of, 
adrenaline   on,   353 
barium   on,   353 
cocaine  on,  353 
physostigmine  on,  339 
apparatus  for  recording,  279 
method  for  recording,  278 
Intestinal    loop,    action    of    nicotine 

on,   307 
Intestinal  loop   oncometer,   223 
Intestinal    segment,    action   of   adre- 
naline,     lobeline,      nicotine, 
pilocarpine  and  atropine,  334 
method   of   recording   contractions 
of,  334 


Intestine,  action  of  adrenaline,  atro- 
pine,  arecoline,  barium  and 
pilocarpine   on,   278 
innervation  of,  336,  384 
Intestines,  action  of  arsenic  on,  460' 
Intraocular    pressure,    action    of    co- 
caine,   barium    and    adrena- 
line on,  353 
action  of  nicotine  on,  308 
method  of  recording,  308 
Intrathoracic     pressure,     action     of 
arecoline  on,  282 
method  for  recording,  282 
Intratracheal  insufflation,  129 
Involuntary      nervous      system,    dia- 
gram of,  384 
Iodide  of  potassium,   457 
Iodine,  tincture  of,  358 
Ipecac,  vomiting,  440 
Iris,  innervation  of,  384,  394 
Iron  rods,   etc.,   supply  of,  487 
Irrigation  of  heart,  221 


Jack  plane,  484 
Jacobson's  nerve,  256,  274 
Jaquet  chronograph,  82 
Jar,   specimen,  46 
Jars  for  anesthetizing  cats,  148 
Jugular  vein,  dissection  for,  91,  142, 
194 
external,  85 


K 


Kelene  tube,  60 

Key,  double  pole  double  throvi-,  35 
simple,  145 
simple   Harvard,   35 
Kidney,  action  of,  agurine  on,  253 
ammonium  acetate  on,  254 
ammonium  chloride  on,  254 
arsenic  on,  460 
caffeine  on,  247,  249 
diuretine  on,  253 
Matthews'  solution  on,  254 
sodium  chloride  on,  254 
sodium  iodide  on,  255 
sodium  nitrate  on,  254 
sodium   phosphate   on,    254 
urea  on,  254 
dissection   for,   128 
left,  exposure  of,  164 
perfusion  of,  342 
Kidney  oncometer,  41,  162,  163 

Eoy's,   42 
Kidney    volume,    action    of    nicotine 

on,   307 
Kits   for  plate  holders,   505 


GENERAL   INDEX 


529 


Kymograph   drum,  method  of   smok- 
ing,  61 
Kymograph,  long  paper,  478-480 
Kymograph  records,  blue  prints,  511 
prints  of,  on  developing  paper,  513 
Kymographs,  45 


Laboratory  supplies  and   equipment, 

dealers  in,  515 
Laboratory     table,     Avith     sink     at- 
tached, 79 
Lachrymal     gland,   innervation      of, 

2G5 
Lacquering,  498 
Lamp,   blast,   482 

spirit,  489 
Langendorff  method  for  perfusion  of 

the  excised  heart,  424,  425 
Lantern  slides,  51,  500,  502,  505,  506 
frame  for  making  mats  for,  507 
staining  of,  508 
Laryngeal  nerve,   superior,  139 
Latent  period  of  cardiac  sympathetic 

nerves,    157 
Lathe,  477,  488 
Left    pulmonary      artery,    dissection 

for,  110,  166 
Left  pulmonary  vein,  dissection  for, 

110,  166 
Leg  volume,  action  of  digitoxin  and 

strojjhanthin   on,   420 
Lenses,  500 
Lever,  frog  heart,  66 
Levers,    heart,   for   dog,    154 
Levulose,   action   of,  on  Ivmph  flow, 

384 
Light,  arc,  for  copying,  501,  502,  506 
Light,  arc,  for  laboratory,  472 
Lingual  nerve,  266,  274 
Liquor  cresolis  compositus,  357 
List  of  apparatus,  permanent,  34 
List     of     dealers     in     supplies     and 

equipment,  515 
List  of  equipment  for  the  shop,  479 
Liver,  166 

action  of  adrenaline   on,  417 
tetramethylammonium  chloride  on, 

423' 
innervation   of,   384 
Liver  oncometer,  brass,  422 

Edmund's,    416 
Lobcline,    action    of,    after    heroine, 
327 
on   bladder,   blood-pressure,    res- 
piration and  pupil,  325 
on  frog  or  turtle  heart,  322,  323 
on  intestinal  segment,   334 
on   turtle   lung,   322,   324 
on  uterine  strip,  332,  333 


Local  anesthesia,  etliyl  chloride,  64 
Locke's   solution,  52 
Lodal,  337 

action    of,    on    blood-pressure    and 
bronchioles,   296 
Long    paper    kymographs,    478,    479, 

480 
Longitudinal  sinus,   105 
Lung,  left,  position  of,  166 
movements  of,  110 
turtle,  action  of  codeine  on,  215 
turtle,    action    of    pilocarpine    on, 
274 
Lung  shield,  208,  209 
Lung  tracings  from  a  turtle,  260-264 
Lung     volume     changes,     recording, 

196,  206,  210 
Lungs,  inflation  of,  197 

innervation    of,    384 
Lungs  of  turtle,  260-264 

innervation  of,  260,   261,  263,   264 
Lymph  hearts,  action  of  chloroform 

on,   70 
Lymph  heart  beats,  action  of  curara 

on,   255 
Lymph  sac,  injections  into,  134 
Lymphatic  system  in  cat,  386 
Lysol,  357 


M 


Machine     for     artificial  respiration, 

473-477 
Machine,   milling,   488 
Magnesium,   anesthesia,  460 

antagonism  of  calcium,  460 
Magnesium   sulphate,   466 
Mammary  artery,  194 
Mammary  vessels,   109,   166 
Manometer,    membrane,    139 
substitute  for,   141 
mercury,  37 
Mat  trimming  frame,  507 
Material   supplied  by   dealers,   515 
Mats   for  lantern   slides,   507 
Mechanical   procedures,   489 
Meckel 's   ganglion,   265 
Mediastinum,   166 
Mediastinum,  anterior,  110,  207 
Medicine  dropper,  68 
Medicine,  method  of  giving  to   dog, 

234 
Meningitis,   360 
Mercury  bulb,  206 
Mercury  vapor  lamps,  506 
Method,     Barbour's     for     recording 

uterine      contractions,     363, 

364 
Langendorff,      for     perfusion      of 

heart,  424,  425 


530 


GEl^ERAL   INDEX 


Method     for,   adjusting     plethysmo- 
graph  on  hind  limb,  304 
generating  oxygen,   185 
recording,     pulmonary    blood-pres- 
sure, 310-318 
oxygen  consumj)tion,  180-184 
Method   of,   observing   capillary   cir- 
culation, 262,  263 
perfusing  excised  kidney,  342,  343 
pithing  a  dog  or  cat,  291-294 
Metol  hydrochinon   developer,   504 
Metronome,  80 

Migraine,  action  of  aspirin  on,  451 
Milling  machine,  488 
Moist  chamber,  Harvard,  57 
Monkey  wrench,  485 
Moreau's  experiment,  466,  476 
Morphine,   action   of,   on   blood-pres- 
sure and  respiration,  177 
on  bronchioles,   194,   199 
on  cat,  177 
on  dog,  175,  204 
on  frog,  172 

on  oxygen  consumption,  177,  191 
on  pupils,  175 
do    not    give    to    animals    without 

special  reason,  354 
dose  of,  for  dog,  175 
excretion  of,  175 
Motor   areas,    action    of,    chloroform 
on,  103 
ether  on,   103 
ethyl  bromide  on,  103" 
exposure  of,  103 
in   dog's  brain,   106 
stimulation   of,    104 
Mouth  gag,  235 

Muscarine,  action  of,  on  bronchioles, 
bladder   and   blood-pressure, 
214,  295 
on  intestinal   contractions,   335 
on  turtle's  lung,   336 
Muscle,  action  of  veratrine  on,  434 
arid  nerve,  action  of,  atropine  on, 
269 
action  of  caffeine  on,  243 
longus  colli,  193 
nerve  preparation,  243 
Muscular    work,    action   of,    caffeine 
on,  245 
cocaine  on,  352 
Muzzle,  for  dog  for  anesthesia,  357, 

358 
Mydriatics,  273 
Mylohyoid  muscle,  267 
Myocardiograph,  149 
Myocardiographic  tracings,  action  of, 
alcohol,  147 
brandy,   147 


Myocardiographic  tracings, 
action  of — Cont'd, 
whiskey,  147 
wine,  147 
Myotics,  273 

N 
Nails,  480 
Narcotine,  action  of,  on  bronchioles, 

194,  203 
Needle  holder,  50 
Needles,  large,  195 
Nerve,  cervical  sympathetic,   142 
chain,   sympathetic,   282,   384 
conductivity  and  irritability,  57 
depressor,  in  rabbit,  247 
erigens,    282,    384 
inferior  laryngeal,  142 
muscle  preparation,  243 
optic,  272,  319,  384 
phrenic,  in  a  dog,  142,  193 
pudic,  282 

superior  laryngeal,  139,  247 
vago-sympathetic,    in   dog,    142 

in  frog,  133 
vagus,   142,   154,  166,   247 
vagus,  in  frog,  65 
Nerve   supply  to   intestine,   336,   384 
Nerves,     cardiac     sympathetic,   142, 
147,  154,  155 
intraocular,  318,  319,  394 

action    of    nicotine,   pilocarpine, 
and  atropine  on,  318,  320 
of  brachial  plexus,  142 
of  frog's  heart,  65,  240 
thoracic  sympathetic,  166 
to  lachrymal  gland,  265,  384 
to   salivary  glands,   dog,  257 
Nervous     system,     involuntary,   dia- 
gram of,  384 
sympathetic,  diagram  of  384 
Nicotine,    action    of,    on    blood-pres- 
sure, respiration,  limb  vol- 
ume and  intestinal  contrac- 
tion, 304,  305,  307,  309 
on    heart    and    vagus    nerves    in 

frog,  300 
on    heart    and   vagus   nerves    in 

turtle,  301,  337 
on  intestinal  segment,  334 
on  intraocular  pressure,  307,  308 
on      pulmonary      blood-pressure, 

310-318 
on  pupil,  306 

on  turtle's  lungs,  302,  303 
on  uterine  strip,  332,  333 
general  action  on  frog,  300 
Nitrite,  amyl,  general   action,  404 
of    sodium,    action    of,    on    frog's 

blood-vessels,  458 
sodium,  general  action,  404 


GENERAL    INDEX 


531 


Nitrites,  action  on  bronchioles,  400 
Nitroj^en,   cffoct   on    anesthesia,    124 
Nitro<>lycerine,   action      of,   on     i)ul- 
nionary  blood-pressure,  415 
general  action,  404 
Nitrous    oxide,    action    of,    in    closed 
anesthesia,  121 
on  frog,   113,   117,   118 
on  guinea  pig,  117,  118 
on  kitten,  117 
on  pup,   117 
on  rat,  117 

on  respiration,  126,  131 
apparatus    for    administering,    130 
method  for  making,  115 
some    dogs   do   not   take   well,   357 
tank   yoke,    115,    116 
Normal  salt  solution,  52 
Note  book,  permanent,  50 
Novocaine,    local    anesthetic    action, 
351 
spinal  anesthesia,  356 
Nulling  tool,  488 

O 

Oesophageal    contractions,    137    {see 

Esophageal   contractions) 
Oil  can,  484 
Oncometer,  128,  129,  160 
brass,  422 

brass,  for  spleen,  421 
Edmund's  416 
for  intestinal  loop,  223 
kidney,    41,    162 
Eoy's,  42 
spleen,   160,  161 
Oncometers,  method  for  making,  491 
Opening  of  chest,  102,  108,  109 
Operating,    table    arranged   for,    123 
Ophthalmoscope,    169-171 
Optic  lobes,  removal  of,  in  frog,  56 
Optic  nerve,  dissection  for,  272,  319 
Oxygen,   action   of,   on   frog,   113 

method  for  generating,  185 
Oxygen     consumption,      action       of, 
j3-tetrahydranaphthylamine 
on,  453 
cyanides  on,  441 
morphine  on,  228 
nicotine,    plioearpine    and    atro- 

jjine  on,  318 
recording  rate  of,  180,  181 
strychnine  on,  226,  229 
Oxygen    tanks,    i^ressure    in,    113 
yoke  for,   115 


Pancreas,   dissection    of,   for      ducts, 
267,  276,   278 


Pancreas — Cont  M. 
dissection  for,  128 
innervation  of,  384 
Pancreatic    ducts,    insertion    of    can- 
nula in,  276,   278 
Pancreatic  ducts,  252,  276,  278 
Pancreatic    secretion,    action    of    at- 
ropine on,  270,  272 
Pantopon,  action   of,  on  bronchioles, 

194,  200 
Paraldehyde,  action  of,  on  frog,  168 

dose  of,  for  cat  or  rabbit,  254 
Passing  catheter,  217 
Paul  Bert 's  experiment,  120 
Pelvic    (erigens)    nerves,   282,   384 
Pelvic  organs  in  dog,  216 
Penis  muscle,   retractor,  innervation 

of,  282 
Peptone,  action  on  temperature,  451 
Perfusion  of  excised  kidney,  342 

apparatus  for,  343 
Perfusion  of  frog's  vessels,  458 
Perfusion      of     heart,     Langendorff, 

424,  425 
Pericardium,   110 
opening  of,  166 
Permanent  note  book,   50 
Peronine,   action  of,   on   bronchioles, 

194,  201 
Pharmacology  and  dissection  of  eve, 

394 
Phases,    two,    of    adrenaline    action, 

166 
Phenacetine,  action  on   fever,  451 
Phenol,  antidote  for,  454,  456 
general  action  of,  on  dog,  454 
general  action  of,  on  frog,  454 
Phenylsalicylate,  absorption  and  ex- 
cretion, 452 
Phloridzin,  glycosuria,  457 
Photography,  500 

Phrenic  nerve,  in  dog,  193,  207,  268 
Phrenic   nerves,    dissection   for,    110, 

143 
Phrenic  nerves,  section  of,  102 
Physostigmine,   action   of,   on  blood- 
pressure,      respiration      and 
bladder    contractions,    346 
on     blood-pressure,     respiration, 

intestinal  contractions,  339 
on  frog's  heart,  337 
on   ring   of   frog's   stomach,   337 
on  the  pupil,  350 
on  turtle's  heart,  338 
on  turtle's  lung,  338 
Picrotoxine,     action     of,     on     blood- 
pressure,    233 
on  frog,  231,  232 
on   respiration,  233 


532 


GE^^ERAL   IISTDEX 


Pigeon,  brain  of,  173,  174 

semicircular  canals  of,  174 
Pilocarpine,    action    of,    on    adrenal 
glands,   278 
on  bladder,   278 
on  bronchioles,  287,  295 
on      frog's      heart     and      vagus 

nerves,  273 
on     frog 's     retinal     circulation, 

274 
on  intestinal  contraction,  blood- 
pressure      and      respiration, 
283 
on  intestinal  segment,  334 
on   pancreatic   secretion,   275 
on  pupil,  275 
on  rate  of  oxvgen  consumption, 

283 
on   salivary   secretion,   275 
on  turtle  lung,  274 
on  uterine  strip,  332,  333 
Pipe  cutter,  487 
Pipe,  gas,  fittings,  485-487 
Pipe  stock  and  dies,  485 
Pithing    a    dog    or   cat,    method    for, 

291-294 
Pithing  a  frog,  method  of,  56 
Pituitrin,   action   of,    on   bronchioles 
and  blood-pressure,  391 
on  capillary   circulation,   387 
on  frog  or  turtle  heart,  388 
on    intestinal    contractions,    392 
on  lymph  flow,  384 
on      pulmonary      blood-pressure, 

384 
on  turtle  lung,  388 
on  urine  secretion,   392 
on  uterine   strip,  390 
on  uterus  in  situ,  382,  389 
Planes,  484 
Plethysmograph,  398 

action   of  amylnitrite   with,   397 
Plethysmograph  for  dog's  hind  limb, 

304 
Pleura,  parietal,   208,  209 
Plexus,   Auerbach's,  336 
Meissner's,   336 
pelvic,  384 
vesical,  384 
Pliers,  479,  485 

Points,  writing,  adjustment  of,  98 
Potassium     chloride,    action    of,    on 

heart,  424 
Potassium    iodide,    absorption,    excre- 
tion,  457 
Preparation,  (gastrocnemius)  muscle 

and  nerve,  243 
Pressure,  air,  negative,  474,  475 
positive,  474,  475 


Pressure — Cont  'd. 

intraocular,   method    of   recording, 

308 
of     air     for     intratracheal     insuf- 
flation,   132 
pulmonary,  action  of  nicotine,  ad- 
renaline, barium  on,  310-318 
method   of   recording,    310-314 
Pressure  bottle,  on  pulley,  97 
Print,  paper,  blue,  510,  511 
Printing  blue  prints  in  sunlight,  511 
Printing  frames  for  blue  prints,  511 
Printing  paper,   508 
Prints,  blue,  51,  510 

bromide  solution  for,  509 
developer  for,  508,  509 
developing,  509 
drying  and  mounting,  510 
fixer  for,  509 
fixing,  510 
Print  trimmer,   63 
Probe,   dissecting,  49 
Prussic  acid   (hydrocyanic),  441 
Pudic  nerve,  282 

Pulmonary     artery,     dissection     for, 
306,  312,  313,  314 
special   cannulas   for,   315 
Pulmonary  blood-pressure,  415 

action  of  ergamine  on,  369,  372 
Punch  for  metal,  485 
Puncturing    spinal    canal,    349,    356, 

359 
Pupil,   action   of,  adrenaline   on,   272 
atropine  on,  269 
cocaine  on,  350 
nicotine  on,  306 
physostigmine  on,  350 
pilocarpine    on,    275 
sympathetic  on,  100 
Pupils,    action   of   morphine   on,    190 
Pyro   developer,  503 

Q 

Quinine,   action  of,   on   fever,  451 
on  frog  or  turtle  heart,  447 
on   white    corpuscle,    Binz's    ex- 
periment, 447 


E 


Eabbit,  action  of,  agurine  on,  253 
diuretine  on,  253 
caffeine,  diuresis  in,  247 
cervical  nerves  in,  247 
depressor  nerves  in,  247 
doses  of  urethane  for,  247 
etherization   of,   247 
uterine  strip,  332,  333 


CxENERAL   INDEX 


Hat,    uetion    of,    curbou    dioxiilc    on, 
117 
ethyl  cliloridc   on,   117 
increased    atiiios])heric    pressure 

on,   117 
nitrous  oxide  on,   117 
Rate   of   oxygen  consumption,   appa- 
ratus for,   180,  181 
Reaction  time,  action  of,  caffeine  on, 
244 
strychnine  on,  230 
whiskey  on,  144 
Recorder  for- drops  of  urine  flow,  249 
Recording,       bladder       contractions, 
mercury  bulb   for,    188,   206 
bladder      contractions,      apparatus 

for,  207 
contractions  of  intestinal  segment, 

334 
convulsions  in  a  frog,  218 
turtle  lung  tracings,  260-264 
uterine  strip  contractions,  appara- 
tus for,  333 
Records,     apparatus     arranged     for 

several  on  drum,  165 
Rectum,  innervation  of,  384 
Reducing   bath    for    slides    or    nega- 
tives,  505 
Reducing  bodies,  Fehling's  test  for, 

176 
Reservoir  for  gas,  186 
Respiration,  action   of,  carbon   diox- 
ide on,   117 
nitrous   oxide   on,    126 
Cheyne-Stokes,   176,   355 
recording,  97,  98 
recording,   Cushny  's   method,   99 
Resuscitation  of  dog,  102,  140 
Retinal   circulation,   action  of,   chlo- 
ral on,  169 
pilocarpine,    arecoline    and    atro- 
pine on,  274 
seen  with  ophthalmoscope,  170,  171 
Retinal    corpuscles,    action    of   amyl- 

nitrite    on,   400 
Retinal    vessels,    action    of    amylni- 

trite  on,  401 
Retractor  penis   muscle,   innervation 

of,   282 
Rhubarb,  466 

Ring  of  frog's  stomach,  336 
Ringer's  solution,   52 
Risus   sardonicus,   224 
Rods,  brass,  480,  482 
Room  for  the  shop,  470 
Rooster's  comb,  action   of  ergot   on, 

360 
Rouge,  498 


li'uhlxT     dam,     attaching     to     stetlio- 
graph,  484 
attaching  screw  or  tack  to,  meth- 
od of,  484 

S 

Salivary  ducts  and  nerves,  257,  266 

Salivary   glands,   action   of  nicotine, 
pilocarpine,      and      atropine 
on,  318 
dissection  to  show,  274 
general  plan  of  innervation,  274 

Salol,  452 

Salt  solution,  52 

Saphenous  nerve,  93 

Saw,  hack,  479,  488 
hand,  479 
hand  bandage,  108 

Scalpel,  49 

Sciatic    nerve    carries    sweat    nerves 
to  foot,  271 

Sciatic   nerve   stimulation,   effect    on 
blood-pressure,   249 
effect  on  respiration,  249,  258 

Sciatic    nerves,    dissection    for,    237 
stimulation  of,  237 

Scissors,  dissecting,  49 

Scopolamine,  action  of,  on  frog,  273 

Scratch    awl,   485 

Screw,    wood    or    metal     (machine), 
485 

Screw   drivers,  479 

Secretion     of     pancreas,     how     con- 
trolled, 268 
action  of  atropine  on,  270 

Secretion   of  salivary   glands,  action 
of  atropine  on,  270 

Section  of  the  phrenic  nerves,  179 

Sensation   not   prevented  by  curara, 
258 

Serrefine,  48 

Shaper    (planer),  488 

Shield,   lung,    208,   209 

Shielded   electrodes,   38 

Shock,    action,    vaso-constrictor   cen- 
ter in,  166 

Shock,  rabbit 's  ears  in,  166 

Shop  work,  470 

Signal  magnet.  Hale 's,  35 
Harvard,    35 
manometer,  37 

Simple   key,  145 

Simplex  heater,  487 

Sinus,  longitudinal,  105 

Skull   of   cat,  mesial   section    of,    179 
u])per  surface  of,  178 

Small  electric  heater,  487 

Small  vise,  479 

Smoking   drums,   61 


534 


GENEKAL   INDEX 


Snips,    tinners,    104,   479 
Sodium  citrate   solution,   53 

cyanide,   general   action,  404,  441- 

445 
hydroxide,  462 

nitrite,  action  of,  on  frog's  blood- 
vessels, 458 
action    of    on    perfused    kidney, 

342 
action  of  on  ring  of  frog's  stom- 
ach, 337 
orthovanadate,   action   of,   on   per- 
fused kidney,  345 
sulphate,  454 

diuresis,  249,  251 
sulphide,  441 
Sodium-theobromine-acetate,   253 
Sodium- theobromine-salicylate,  253 
Soldering,  483,  489-492 
acid,  483,  489 
aluminum,  489 
tracheal  cannula,  490 
Solution,  Locke 's,  52 

NaOH   for    closed   anesthesia,    122 
normal  salt,  52 
Ringer's,  52 
sodium  citrate,  53 
Tyrode's,  52 
Solutions,  injection  of,  94 
Somnoform,   121 
Special  apparatus,  52 

for   obtaining  bronchiole   tracings, 
288,   289 
Speed  lathe,  488 

Sphygmograph,     action     of     amylni- 
trite  on,  400 
Dudgeon's,  399 
Spinal  anesthesia,  356 
Spinal  canal,  puncture  of,  349,  359 
Spinal    dog,    method    of    preparing, 

194,  291-294 
Spinal  ganglion,  349 
Spinning   attachment   for   drum,  436 
Splanchnic     nerves,     dissection     for, 
166,   167 
functions   of,   167 
Spleen,  dissection  for,  128 
innervation   of,   384 
oncometer,    160,   161,   421 

method  of  applying,  161 
volume,  action  of  nicotine  on,  307, 
309 
Squares,  try  and  carpenter 's,  485 
Staining  lantern  slides,  508 
Stand,   copying,   501 
Stands,  castings  for,  496 

making,  496,  497 
Starch    granules,    injected    into    ca- 
rotid artery,  197 


Stellate   ganglion,   154 
Sterilization  of  hands,  358 
Stethograph   drum,  41 
Stillson  wrenches,  487 
Stimulation  of  motor  areas,  104 
Stocks  and  dies,  485 
Stomach,    innervation    of,    384 
Stomach  tube,  passing  in  a  dog,  234 
Straight  cannula,  glass,  107 
Strophanthin,  action  of,  on  perfused 
heart,  424,  425 
on  pulmonary  blood-pressure,  415 
general  action,  420 
Strychnine,  action  of,  on  blood-pres- 
sure, 222 
on  frog,  217 
on        frog's        cardio-inhibitory 

nerves,  220 
on  frog's  heart,  220 
on  oxygen  consumption,  226 
on  reaction  time,  230 
on  respiration,   222 
on  special  senses,  231 
on  turtle's  heart,  220 
on  vagus  nerve  in  turtle 's  heart, 
220,  222 
and    eurara,    action    of,    on    blood- 
pressure      and      respiration, 
257 
gastrocnemius  contraction  records, 
218,  219 
Subclavian  ansa,  154 
Subclavian     artery,     dissection     for, 

143 
Subclavian  vein,  142,  194 

dissection  for,  143 
Substitute  for  membrane  manometer, 

141 
Superior  cervical  ganglion,  154,  245, 

265,  274,  394 
Superior  laryngeal  nerve,  139 
Superior  mesenteric   ganglion,   384 
Supplies  and  equipment,  dealers,  515 
Supplies  of  brass,  480 
Supplies  of  iron  rod,  etc.,  487 
Sweat   secretion,   action   of   atropine 

on,  270 
Sympathetic,     cervical     nerves     and 
ganglion,   142 
ganglion,   inferior    cervical,    154 
nerve,  cervical,  in  rabbit,  246 
nerves,  cardiac,  in  cat,   155 
cardiac,  in  frog,  66 
cardiac,  in  turtle,   75 
in  neck  of  rabbit,  247,  248 
to  frog's  heart,  240 
to   heart,   154 
nervous  system,  diagram  of,  384 
thoracic  trunks,  166 
System,  electric  wiring,  471 


GENERAL    INDEX 


535 


T 


Table,  arranged  for  operating,  123 

laboratory,   79 
Tables,  small  supporting,  47 
Tambour,   adjustable,   40,   483 
cheap  form,  484 
Marey,  40 
Tanks,  carbon  dioxide,  116 
nitrous  oxide,  113 
oxygen,  113 
Tape  worms,  230 
Tartar  emetic,  462 
Taste  organs,  351 

Technic    for   inserting    bladder    can- 
nula,  188 
Telephone,    for    reaction    time,    145, 

146 
Temperature,  rectal,  148 
Tetramethylammonium    chloride,    ac- 
tion of,  before  and  after  at- 
ropine,  329 
on     blood-pressure,     respiration, 
bladder  and  pupil,  325,  330, 
331 
on  bronchioles,  331 
Thebaine,  action  of,   on  bronchioles, 
194,  377 
on  frog,  173 
Thoracic  duct,  356,  384,  386 
Thoracic  sympathetic,  166 
Thyroid  gland,  142 
Time  clock.  Harvard,  81 
Time  recording  metronome,   80 
Time   recording  watch,   Lieb-Beckcr, 

80 
Tincture  of  iodine,  358 
Tinner's  snips,  479 
Trachea,  dissection  to  expose,  86 
Tracheal     cannula,     attachment     of 
other  bottle  to,  89 
brass,  39 

insertion  of,  in  dog,  89 
soldering,   490 
Tracing  trimmer,  63 
Tracings    from    turtle's    lungs,    260, 

264 
Transverse  scapular  artery,  194 
Trephine,  105 

Trimethylamine,  action  of,  on  blood- 
pressure,  respiration  and  in- 
testinal    contractions,     339, 
340,  341 
Tripoli,  498 

Trocar   and   cannula,   359 
Try  square,  485 

Tube,  stomach,  passing  in  a  dog,  234 
into  larynx,  235 
to  pass  through  chest,  196 
Tubing,  brass,  .480 


Turning  attachments,  488 
Turning  lathe,  477,  488 

motor  driven,  488 
Turtle  board,  operating,  46 
Turtle     lung    tracings,    method     for 

making,  260-264 
Turtle's  heart,   74 

action  of,  alcohol  on,   135 
chloroform  on,  76 
ether  on,   71 
hydrastine  on,  241 
and  vagus  nerves,  action   of  atro- 
pine on,  269 
exposure  of,  circular  saw  for,  73 
method   for   recording  heart    trac- 
ings, 72,  73 
sympathetic  nerves  to,  77 
Turtles,    list    of    dealers    supplying, 

515 
Turtle 's    lungs,    action    of,    lobeline 
on,  323,  324 
nicotine  on,   302,   303 
physostigmine  on,  338 
dissection  to   show,  261 
Turtle's  vagus  nerve,  71,  73,  75 
Tyramine,  371 

action    of,    on    blood-pressure,    370 
on   capillaries,   363 
Tyrode  's  solution,  52 


U 


Ureter,  innervation  of,  384 
Ureteral  cannula,  glass,  225 
Ureters,  dissection  for,   226 
Urethane,  action  of,  on  frog,  168 
dose  for  cat,  254 
dose  for  rabbit,   247,   254 
Urine,  action  of  curara  on  secretion 
of,   257 
collecting    from    bladder    cannula, 

188 
testing  for  glucose,  189,  248 
Urine    flow,    action    of,    caffeine    on, 
247,   249 
chloral  on,  252 
Matthews'  solution  on,  254 
sodium  iodide  on,  255 
sodium  sulphate   on,  251 
urea  on,  254 
drop  recorder  for,  249,  250 
normal  rate   of,  250 
Uterine       contractions,        Barbour's 
method    of    recording,    363, 
364 
method   of   recording,  333 
method  of  recording  in  situ,  382 
Uterine    strip,    action    of,    lobeline, 
nicotine,      and      pilocarpine 
on,  332,  333 


536 


GENERAL    INDEX 


Uterine  strip, 

action  of — Cont  'd. 

pituitrin   on,  390 
method   of   recording   contractions 
of,  333,  380,  381' 
Uterus,  action  of,  barium  on,  284 
erganiine     and     ergotoxine     on, 

363,   366 
ergot  on,  381 
dissection  for,  230 
innervation  of,  38-1 


V 


Vacuum,  pump,  473,  474 
Vagi,    action    of,    on    turtle's    lung, 
260-264 
section    of,    effect    on    respiration, 
236 
Vago-sympathetic  nerve  in  frog,  65, 

66,   133 
Vagus    and    sympathetic    nerves    in 

the  turtle,   75 
Vagus    and    sympathetic    nerves    to 

the   heart,   154 
Vagus  nerve,   dissection  for,  in  dog, 
85,  90,  142,  194 
in  frog,  65 
in  turtle,  heart,  71,  135 
method    of    stimulating    in    turtle, 
72,   75 
Vagus  nerves,  action  of  atropine  on, 

269,  273 
Valves  for  artificial  respiration  ma- 

chiues,   473-477 
Vanadium,   action  of,   on  pulmonary 
blood-pressure,   394 
general   action,   462-465 
Varnish  for  tracings,  62 
Varnishing  pan  for  varnishing  long 

tracings,  63 
Varnishing  rack  and  pan,  62 
Vein,  external  jugular,  91 
femoral,  dissection  for,   94 
left  pulmonary,   112 
saphenous,  93 

insertion  of  cannula  in,  93 
subclavian,  142,   143,  155,  194 
Veins,  jugular,  142,  192,  194 

ligation  of,   193 
Veratrine,   action   of,   on   blood-pres- 
sure,  respiration   and  intes- 
tinal  contractions,   437 


Veratrine, 

action  of — Cont  'd. 

on  frog's  skeletal  muscle,  434 
on  turtle's  lung,  437,  438 
frog,   general   action,   433 
frog    or    turtle    heart,    action    on, 

434,  435 
heart  tracings  and  blood-pressure, 
440 
Vertebral  artery,  193,  195 
Vessels,  blood,   of   a   frog,  perfusion 

of,  458,  459 
Vieussenii,   annulus  of,   143 
Visceral   organs,   dissection    of,    dog, 

167 
Vise,  large,  487 

small,  479 
Vision,  action  of  amylnitrite  on,  403 
Vitality  of  spinal  dog,  205 
Vomiting,  apomorj)hine,  440 
ipecac  in,  440 
tartar  emetic  in,  462 

W 

Wharton's   duct,    257,   259,   266,   274 
dissections  for,  266,  274 

Wheel,  emery,  487,  495 

Whiskey,    action    of,    on    blood-pres- 
sure  and   respiration,   136 

Wine,    action    of,    on    blood-pressure 
and  respiration,  136 

Wire,  copper,  484 

Wire  gauge,  487 

Wiring   system    for    electric    current 
for  laboratory,  471 

Wood  former,  488 

Wood  lathe,  488 

Work  bench,  485 

Worms,  tape,  230 

Woulff,  ether  bottle,  three  necked,  38 

Wrenches,  485 
Stillson,  487 

Writing  points,  adjustment  of,  98 

Y 

Yeast,  fermentation  by,  157 
Yokes  for  gas  tanks,  115,  116 


Zinc  sulphate  solution,  for  boot  elec- 
trodes,  59 


Date  Due 

^(kl^ 

^ 

ifirw 

iBw 

^> 

